The DOI matches its Crossref record; 232 of the 233 references it cites were found in a registry or an index; 71 of the 204 sources its claims cite were checked for support.
Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity
Open accessAbstract
Gonadal hormones play a key role in the establishment, activation, and regulation of the hypothalamic-pituitary-adrenal (HPA) axis. By influencing the response and sensitivity to releasing factors, neurotransmitters, and hormones, gonadal steroids help orchestrate the gain of the HPA axis to fine-tune the levels of stress hormones in the general circulation. From early life to adulthood, gonadal steroids can differentially affect the HPA axis, resulting in sex differences in the responsivity of this axis. The HPA axis influences many physiological functions making an organism's response to changes in the environment appropriate for its reproductive status. Although the acute HPA response to stressors is a beneficial response, constant activation of this circuitry by chronic or traumatic stressful episodes may lead to a dysregulation of the HPA axis and cause pathology. Compared to males, female mice and rats show a more robust HPA axis response, as a result of circulating estradiol levels which elevate stress hormone levels during non-threatening situations, and during and after stressors. Fluctuating levels of gonadal steroids in females across the estrous cycle are a major factor contributing to sex differences in the robustness of HPA activity in females compared to males. Moreover, gonadal steroids may also contribute to epigenetic and organizational influences on the HPA axis even before puberty. Correspondingly, crosstalk between the hypothalamic-pituitary-gonadal (HPG) and HPA axes could lead to abnormalities of stress responses. In humans, a dysregulated stress response is one of the most common symptoms seen across many neuropsychiatric disorders, and as a result, such interactions may exacerbate peripheral pathologies. In this review, we discuss the HPA and HPG axes and review how gonadal steroids interact with the HPA axis to regulate the stress circuitry during all stages in life.
Overview
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Written from the paper’s full text.
TL;DR
This review argues that gonadal steroids shape hypothalamic–pituitary–adrenal (HPA) axis activity and stress responsivity across the lifespan, producing stronger stress hormone responses in female rodents than in males. It synthesizes evidence that hypothalamic–pituitary–gonadal (HPG) and HPA crosstalk, including estrogen receptor and neuropeptide mechanisms, contributes to sex differences relevant to stress-related pathology.
Key findings
- Female rodents generally mount larger and longer-lasting HPA responses than males; estradiol elevates stress hormone levels, and estrous cycle stage matters, with proestrus associated with higher stress hormone levels and greater anxiety-like responses than estrus.
- Gonadal steroids modulate the HPA axis at multiple levels: in male rats, gonadectomy increases while androgen replacement blunts ACTH and corticosterone responses to stress; in females, ovariectomy reduces and estradiol treatment increases HPA gain.
- Estrogen receptor β (ERβ) appears to reduce HPA reactivity, whereas ERα may increase it. ERβ is expressed in PVN CRH neurons at 5% co-localization in the medial PVN and 60–80% in the caudolateral division, and about 85% of PVN oxytocin neurons express ERβ in rats.
- Developmental organization by perinatal testosterone and its metabolites contributes to adult sex differences; pre-pubertal male rats take 30–45 minutes longer than adults to return to baseline after acute stress, and neonatal castration or aromatase blockade can feminize adult HPA responses.
Methods
- Narrative review of the HPA and HPG axes, integrating rodent and human literature rather than presenting primary experimental data.
- Covers HPA components (PVN, pituitary, adrenal), negative feedback, gonadal steroid receptors, neuropeptidergic regulation, steroid metabolism, and sexual differentiation.
- Main analysis is qualitative synthesis of cited studies; no systematic search strategy, meta-analysis, or formal quality assessment is described.
Limitations
- The paper states that mechanisms of gonadal steroid regulation of AVP remain unresolved, that the low ERβ co-localization with CRH neurons is a conundrum, and that interactions between steroid receptors on neuropeptide promoters and co-regulatory proteins are not yet described.
- The paper notes that upstream regulators of the HPA axis are much less understood, including prefrontal cortex and extra-hypothalamic regions such as the bed nucleus of the stria terminalis.
- Evident from the text: the evidence base is heavily rodent-focused, especially rats, with human relevance often speculative; as a narrative review, it does not systematically assess study quality or publication bias.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
50 No full text of the sources · 40 Own interpretation · 30 Partly supported · 24 Supported · 19 No basis given · 17 Not checked yet · 12 Sources not found · 10 Supported so far · 4 Not supported · 1 Couldn’t confirm · accuracy not yet measured
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“The estradiol-dependent regulation of CRH neurons in the PVN is thought to be regulated by the estrogen receptor β”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > The pituitary gland
What the sources say
- Disputedcites Lund, Hinds, & Handa, 2006 sourceExperimental — accuracy not yet measured
The Discussion says that estradiol (E2) enhances the stress response through an ERα-dependent mechanism, not ERβ. It also says that only a small population of neuroendocrine CRH neurons in the PVN appear to contain ERβ; the proposed ERβ pathways concern inhibition by other compounds. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Disputed
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Peripheral administration of the estrogen receptor β agonist, R-DPN, prevented the increased HPA axis reactivity and increased anxiety-like behaviors in female rats in response to the implantation of a wax pellet containing a GR agonist, adjacent to the central nucleus of the amygdala (Weiser, Foradori, & Handa, 2010).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > Negative feedback and corticosteroid receptors
What the sources say
- Disputedcites Weiser, Foradori, & Handa, 2010 sourceExperimental — accuracy not yet measured
The Results (§2) report that peripheral S-DPN blocked the anxiety-like behaviors and increased stress-induced corticosterone associated with RU28362 implants. But the claim names R-DPN. Drug treatments (§4; page not provided) explicitly states that only the S-enantiomer was tested. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Disputed
Every source the paper cites for this claim was checked and supports it.
In the paper
“the mechanisms to cope with stressors differ between males and females”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Introduction
What the sources say
- Supportedcites Bale & Epperson, 2015 source
The paper’s discussion of stress responses (labeled Abstract in our copy) says female rodents use more passive strategies than males and that passive coping responses are more common in women. The Conclusions also state that males and females respond differently to stress. (LLM, conf=0.92)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“OT and CRHR2 fibers present in the BnST originated in the PVN.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > The pituitary gland
What the sources say
- Partly supportedcites Dabrowska et al., 2011 sourceExperimental — accuracy not yet measured
The Results report PVN-labeled fibers in the BNST that co-localized with both OT and CRFR2. The Discussion specifies that OT fibers in the BNST originate from PVN neurons “at least partially,” so the paper does not establish a PVN origin for all such fibers. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The Crh gene and promoter activity have been shown to be regulated by estrogens”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > The pituitary gland
What the sources say
- Not matchedcites Lalmansingh & Uht, 2008
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Supportedcites Miller, Suzuki, Miller, Handa, & Uht, 2004 source
The Discussion reports that ERβ isoforms substantially regulate the CRH promoter. It also reports E2-stimulated CRH transcription, while the ERβ isoform results describe the CRH gene’s response to E2. The effects depend on receptor isoform and experimental context. (LLM, conf=0.89)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“CORT can also act indirectly in extra-PVN regions expressing MR and GR, such as the hippocampus, to inhibit the secretion of CORT (Akana, Cascio, Du, Levin, & Dallman, 1986; Dallman et al., 1987; Kovacs, Foldes, & Sawchenko, 2000; Sawchenko, 1987) through a trans-synaptic mechanism (Herman et al., 2016).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > Negative feedback and corticosteroid receptors
What the sources say
- Not checked — no full text of the sourcecites Akana, Cascio, Du, Levin, & Dallman, 1986 source
- Not checked — no full text of the sourcecites Dallman et al., 1987 source
- Supportedcites Herman et al., 2016 source
In “The ‘falling’ phase: transsynaptic inhibition of the HPA axis,” the paper describes hippocampal projections through GABAergic neurons to inhibit PVN activation and notes that the hippocampus expresses both MR and GR. “Brain glucocorticoid feedback processes” explicitly identifies trans-synaptic modulation through the hippocampus as a route of GR-mediated inhibition. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Mineralocorticoid receptors have a much higher affinity (Kd = 0.5 nM) for CORT than do GRs (Kd =5.0 nM) (De Kloet, Veldhuis, Wagenaars, & Bergink, 1984; De Kloet, Vreugdenhil, Oitzl, & Joels, 1998)”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > Negative feedback and corticosteroid receptors
What the sources say
- Not checked — no full text of the sourcecites De Kloet, Veldhuis, Wagenaars, & Bergink, 1984 source
- Supportedcites De Kloet, Vreugdenhil, Oitzl, & Joels, 1998 source
The section “Corticosteroid receptor diversity in brain and pituitary” states that MRs bind corticosterone with 10-fold higher affinity than GRs and gives an MR dissociation constant of approximately 0.5 nM, measured at 4°C. That ratio implies the cited GR value of approximately 5.0 nM. (LLM, conf=0.93)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Stinnett et al. (2015), indicated higher Crh-BP mRNA transcripts in pituitary from female mice versus male mice, even after restraint stress”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > The pituitary gland
What the sources say
- Supportedcites Stinnett, Westphal, & Seasholtz, 2015 source
The Results section reports that basal pituitary CRH-BP mRNA was more than 200-fold higher in female mice than in males. Restraint stress increased expression 11.8-fold in females and 3.2-fold in males, so female levels remained higher after stress. (LLM, conf=0.92)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Dabrowska et al. (2011) have shown that not only does the BnST interact with the PVN, but also vice versa, presumably through an OT and CRHR2 mechanism”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > The pituitary gland
What the sources say
- Supportedcites Dabrowska et al., 2011 source
The Discussion describes BNST input to the PVN and suggests reciprocal input from the PVN to the BNST via CRFR2/OT-positive fibers. The Results report tracing evidence for OT- and CRFR2-positive fibers from the PVN in the BNST. The claim’s “presumably” appropriately reflects the proposed mechanism; page numbers are not provided in our copy. (LLM, conf=0.92)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Additional evidence for CORT acting directly on PVN neurons comes from studies where targeted deletion of GR in the PVN increased CRH expression and CORT and ACTH levels in male mice (Jeanneteau et al., 2012).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > Negative feedback and corticosteroid receptors
What the sources say
- Partly supportedcites Jeanneteau et al., 2012 sourceExperimental — accuracy not yet measured
In “Reduced Expression of the GR in the PVN Disinhibits the HPA Axis,” the paper reports increased PVN CRH and elevated plasma ACTH and corticosterone in GR flox/+;Sim1Cre mice. The Methods specify adult males. The deletion was of one floxed GR allele, producing reduced GR expression rather than complete deletion; Sim1-Cre expression was also not confined to the PVN. (LLM, conf=0.87)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
- It may state two separate claims as one. 59
- Probably not a substantial claim. 20
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“since the PVN selective loss of GR caused a striking increase in HPA reactivity and depression-like behaviors in males but not females (Solomon et al., 2012).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > Negative feedback and corticosteroid receptors
What the sources say
- Disputedcites Solomon et al., 2012 sourceExperimental — accuracy not yet measured
The Results section reports that GR immunoreactivity in the PVN was comparable in knockout and control mice; GR loss was instead observed in the medial prefrontal cortex, hippocampus, and basolateral amygdala. The Discussion supports the male–female difference in HPA function and depression-like behavior, but the claim that selective PVN GR loss caused it is contrary to the reported knockout pattern. (LLM, conf=0.89)
Checked by a reasoning model — may be wrong.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Disputed
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“However, a conundrum arises in that ERβ has not been detected in GnRH neurons of mice, yet they still respond to estradiol (Handa, Ogawa, Wang, & Herbison, 2012).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The hypothalamic–pituitary–gonadal axis > Steroid feedback loop
What the sources say
- Disputedcites Handa, Ogawa, Wang, & Herbison, 2012 sourceExperimental — accuracy not yet measured
In “ERβ and the neural regulation of fertility,” the paper says GnRH neurons express ERβ mRNA and protein in mice—the opposite of the claim that ERβ has not been detected in them. “Potential roles for ERβ expressed by GnRH neurones” also reports that mouse GnRH neurons respond to oestradiol, so the contradiction concerns detection of ERβ, not responsiveness. (LLM, conf=0.94)
Checked by a reasoning model — may be wrong.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Disputed
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Chronic and traumatic stressors, however, have the opposite effect, causing detrimental changes in the brain and other organs, and have been linked to the development of pathology including neuropsychiatric disorders, such as post-traumatic stress disorder, depression, chronic anxiety”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Introduction
What the sources say
- Partly supportedcites Smith & Vale, 2006 sourceExperimental — accuracy not yet measured
The Conclusions (page unavailable) link dysregulation of the stress response to hypertension, affective disorders, and major depression, and discuss stress-related anxiety and energy metabolism. The limbic-system section (page unavailable) suggests a link between the stress system and neuropsychiatric disorders. The copy does not establish that chronic or traumatic stressors cause detrimental changes in the brain and other organs, or specifically link them to PTSD or cardiometabolic disease. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites Levine, Levine, & Levine, 2014 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“on proestrus, 80% of the CRH-BP of the murine female pituitary is present in prolactin-expressing cells, suggesting that high estrogen levels drive the expression of CRH-BP and restrict the amounts of bioactive CRH that can activate corticotrophs.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > The pituitary gland
What the sources say
- Partly supportedcites Speert, McClennen, & Seasholtz, 2002 sourceExperimental — accuracy not yet measured
The cellular-localization results report that approximately 80% of pituitary CRH-BP mRNA signal at proestrus is in prolactin-expressing cells, and the Discussion supports positive estrogen regulation. The paper describes CRH-BP sequestration of CRH as a proposed mechanism, but does not show that 80% of the protein is in those cells or measure a reduction in bioactive CRH available to corticotrophs at proestrus. The indexed passages provide section labels but no page numbers. (LLM, conf=0.82)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“ovariectomy reduces, while estradiol treatment increases, the gain of the HPA axis”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > The adrenal gland
What the sources say
- Not checked — no full text of the sourcecites Lund, Munson, Haldy, & Handa, 2004 source
- Supportedcites Viau & Meaney, 1991 source
The HPA-HPG Interactions section says ovariectomy abolishes the greater stress response seen in female rats and estradiol restores it. The Additional information section also states that ovariectomy decreases ACTH and corticosterone production and that estrogen replacement reverses those effects, supporting the paraphrase about HPA-axis gain. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Thus, these data may indicate that there are other upstream factors involved.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > The pituitary gland
What the sources say
- Partly supportedcites Viau & Meaney, 1991 sourceExperimental — accuracy not yet measured
The Additional information section reports enhanced stress-induced ACTH secretion during early proestrus and proposes changes in norepinephrine-sensitive adrenergic signaling as a possible upstream influence on CRH release. It does not discuss CRH-binding protein or say that the ACTH response conflicts with a CRH-BP restriction of CRH. (LLM, conf=0.84)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The level of CRH-BP is also higher in the murine pituitary and the cells expressing Crh-BP mRNA may also be involved in the regulation of reproductive hormones, such as prolactin and luteinizing hormone β”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > The pituitary gland
What the sources say
- Partly supportedcites Speert, McClennen, & Seasholtz, 2002 sourceExperimental — accuracy not yet measured
The Results section reports higher pituitary CRH-BP expression in female than male mice; the claim does not specify that comparison. The cellular-localization results find CRH-BP mRNA in prolactin-expressing cells and, less frequently, LHβ-expressing cells. The Discussion suggests possible interactions with reproductive endocrine systems but says the significance of LHβ colocalization is unclear; it does not establish regulation of either hormone. (LLM, conf=0.83)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“While GRs are ubiquitously expressed throughout the brain, they are highly expressed in the hippocampus (De Kloet, Vreugdenhil, Oitzl, & Joels, 1998) and hypophysiotropic neurons of the PVN (Kovacs, Foldes, & Sawchenko, 2000; Sawchenko, 1987), two brain regions key to negative feedback.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > Negative feedback and corticosteroid receptors
What the sources say
- Partly supportedcites De Kloet, Vreugdenhil, Oitzl, & Joels, 1998 sourceExperimental — accuracy not yet measured
In “Corticosteroid receptor diversity in brain and pituitary” (page unavailable), the review says GRs are present in hippocampal dentate gyrus neurons and CA1 cells and are widely distributed in the brain. It does not establish that hippocampal GR expression is particularly high. The PVN-neuron clause is attributed to different citations in the citing sentence, not to this paper. (LLM, conf=0.82)
- Partly supportedcites Kovacs, Foldes, & Sawchenko, 2000 sourceExperimental — accuracy not yet measured
The Discussion section ('Possible mechanisms of glucocorticoid effects on CRF and AVP expression'; page unavailable) states that parvocellular neurosecretory neurons express type II glucocorticoid receptors. It does not establish that receptor expression is high in those neurons. The hippocampus portion has a separate citation and is not attributed to this paper. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites Sawchenko, 1987 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The opposite was found when pellets with DPN, the ERβ agonist, were placed in the same region.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > Negative feedback and corticosteroid receptors
What the sources say
- Supportedcites Weiser & Handa, 2009 source
The Results sections on the diurnal rise and restraint stress report that DPN-containing pellets placed just superior to the PVN significantly lowered CORT compared with control pellets. This supports the cited sentence’s contrast with the effects of the ERα agonist. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The differential regulatory effects of ERα and ERβ on AVP could be due to the constitutive activity of ERβ on the Avp promoter (Pak, Chung, Hinds, & Handa, 2007; Shapiro, Xu, & Dorsa, 2000).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Gonadal hormones and neuropeptidergic regulation of the HPA > Steroid hormone control of arginine vasopressin and regulation of the HPA
What the sources say
- Supportedcites Pak, Chung, Hinds, & Handa, 2007 source
The Discussion says ERβ constitutively activates the AVP promoter and describes this as a property not shared by ERα. The section on ligand-dependent and ligand-independent effects also reports increased AVP promoter activity with ERβ1 in neuronal cells. Together, these passages support the proposed explanation for differential regulation; page numbers are not available in the supplied copy. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites Shapiro, Xu, & Dorsa, 2000 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The activity of GnRH is regulated by neurotransmitters, steroid hormones, and growth factors (Watanabe, Fukuda, & Nabekura, 2014).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The hypothalamic–pituitary–gonadal axis > Gonadotropin releasing hormone (GnRH)
What the sources say
- Supportedcites Watanabe, Fukuda, & Nabekura, 2014 source
The Introduction states that GnRH release is closely related to the activity of GnRH neurons, which are regulated by neurotransmitters, steroid hormones, and growth factors. This directly supports the citing sentence’s paraphrase. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“LH stimulates the synthesis of testosterone by Leydig cells (Ramaswamy & Weinbauer, 2014), whereas FSH stimulates sperm cell maturation and supports Sertoli cells.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The hypothalamic–pituitary–gonadal axis > LH and FSH action on steroidogenesis: males
What the sources say
- Supportedcites Ramaswamy & Weinbauer, 2014 source
The citation is attached to the LH clause, not the subsequent FSH clause. The Background passage states that Leydig cells produce testosterone in response to LH signaling; no page number is provided in our copy. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“In the rodent, hypophysiotropic GnRH neurons project to the median eminence where they release GnRH in a regular pulsatile manner (Bakker, Rubin, & Baum, 1999; Herbison, 2016; Jimenez-Linan, Rubin, & King, 1997; Silverman, Kokoris, & Gibson, 1988).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The hypothalamic–pituitary–gonadal axis > Gonadotropin releasing hormone (GnRH)
What the sources say
- Could not verifycites Bakker, Rubin, & Baum, 1999 sourceExperimental — accuracy not yet measured
The Distribution of neurons containing GnRH mRNA section describes ferrets, not neuronal projections in rodents. The Relationship between GnRH mRNA levels and GnRH release after mating section discusses pulsatile LH secretion in ferrets, not regular pulsatile GnRH release in rodents. Searches for rodent projections to the median eminence and pulsatile GnRH release found no passage establishing the claim; page numbers were unavailable in our copy. (LLM, conf=0.76)
- Not checked — no full text of the sourcecites Herbison, 2016 source
- Not checked — no full text of the sourcecites Jimenez-Linan, Rubin, & King, 1997 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Could not verify
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Kisspeptin neurons have been shown to express ERα (Adachi et al., 2007; Clarkson, d’Anglemont de Tassigny, Moreno, Colledge, & Herbison, 2008; Franceschini et al., 2006) and the kisspeptin receptor GPR54 is expressed in GnRH neurons (Clements et al., 2001; Kotani et al., 2001; Muir et al., 2001; Ohtaki et al., 2001).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The hypothalamic–pituitary–gonadal axis > Steroid feedback loop
What the sources say
- Supportedcites Adachi et al., 2007 source
Adachi et al. is cited for the ERα expression clause, not the GPR54 expression clause, which has separate citations. The paper's Abstract and Discussion report that AVPV kisspeptin neurons contain ERα; the Abstract also reports ERα immunoreactivity in most KiSS-1 mRNA-expressing cells in the AVPV and ARC. Page numbers are not supplied in our copy. (LLM, conf=0.94)
- Supportedcites Clarkson, d’Anglemont de Tassigny, Moreno, Colledge, & Herbison, 2008 source
The Clarkson et al. citation is attached to the first clause, about ERα expression in kisspeptin neurons. The Results section reports dual-label evidence that RP3V kisspeptin neurons in mice express ERα; the GPR54 clause is attributed to other citations. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites Franceschini et al., 2006 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Curiously, GnRH receptors have also been described in numerous tissues throughout the body, including the brain (Cheung & Wong, 2008; Wilson et al., 2006), but their functional significance has not been completely determined.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The hypothalamic–pituitary–gonadal axis > GnRH action at the anterior pituitary
What the sources say
- Not checked — no full text of the sourcecites Cheung & Wong, 2008 source
- Supportedcites Wilson et al., 2006 source
The “Functional consequences” section describes GnRH receptors in reproductive and nonreproductive tissues, including the hippocampus, and says it is unclear how receptors throughout the body are engaged. Its summary reports receptors on human brain neurons while stating that the physiological significance of a neuronal response remains to be fully investigated. No page numbers are provided in our copy. (LLM, conf=0.92)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Stimulation of GnRH receptors on gonadotrophs results in elevations in intracellular calcium, which drives the release of LH and FSH by exocytosis into the general circulation to eventually reach the gonads (Duran-Pasten & Fiordelisio, 2013).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The hypothalamic–pituitary–gonadal axis > GnRH action at the anterior pituitary
What the sources say
- Supportedcites Duran-Pasten & Fiordelisio, 2013 source
The Abstract states that GnRH binding to gonadotroph receptors triggers the intracellular Ca2+ elevations needed for secretion and that GnRH-induced Ca2+ signals control LH/FSH exocytosis. The Gonadotrophs Function and Characteristics section likewise says the cytosolic Ca2+ rise triggers gonadotropin exocytosis. The source notes that FSH release is mostly constitutive, but this does not negate the attributed mechanism. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Interestingly, the mRNA transcripts levels of aromatase, 5α-reductase, and CYP7B1 are highly present in the PVN, indicating their potential role in the local metabolism of steroids and further regulation of the HPA axis (Lund, Hinds, & Handa, 2006).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Steroid metabolites and the control of the HPA axis
What the sources say
- Partly supportedcites Lund, Hinds, & Handa, 2006 sourceExperimental — accuracy not yet measured
In “The PVN contains relevant steroid hormone metabolizing enzymes” (page not specified), the authors report detecting aromatase, 5α-reductase, and CYP7B mRNAs in microdissected PVN and suggest that these enzymes could regulate the availability of steroid ligands. The RT-PCR finding establishes presence, not that the transcripts are present at high levels; the proposed contribution to HPA regulation remains a possibility rather than a demonstrated effect of these enzymes. (LLM, conf=0.87)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Arcuate nucleus kisspeptin, neurokinin B, and dynorphin co-expressing neurons initiate pulsatile hormone patterns in the absence of estradiol and are inhibited at low levels of estradiol to account for negative feedback, yet AVPV localized kisspeptin neurons are activated by rising titers of estradiol and initiate the pre-ovulatory surge of LH (Wang, DeFazio, & Moenter, 2016).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The hypothalamic–pituitary–gonadal axis > Steroid feedback loop
What the sources say
- Partly supportedcites Wang, DeFazio, & Moenter, 2016 sourceExperimental — accuracy not yet measured
The Introduction and Discussion (page unavailable) support estradiol-related activation of AVPV kisspeptin neurons and their proposed role in the preovulatory GnRH/LH surge. The Introduction says arcuate kisspeptin neurons may convey negative feedback, but the paper does not establish the claimed KNDy-driven pulses in the absence of estradiol or their inhibition by low estradiol. It also describes the AVPV role as a proposed contribution to the surge, not proof that these neurons initiate it. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“A third neuropeptide dynorphin, has also been found in arcuate nucleus kisspeptin neurons but has an inhibitory effect on GnRH secretion (Plant, 2015).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The hypothalamic–pituitary–gonadal axis > Steroid feedback loop
What the sources say
- Supportedcites Plant, 2015 source
In “Neurobiology of the hypothalamic GnRH pulse generator” (page not provided), Plant reports that arcuate nucleus kisspeptin neurons co-express dynorphin and describes dynorphin as inhibitory to GnRH release. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In the rodent, the absence of testosterone during a critical perinatal period results in the expression of the default program of the brain, which is female-like (McCarthy & Arnold, 2011), whereas perinatal treatment of females with testosterone will defeminize the brain and prevent the expression of female reproductive behaviors in adulthood.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Sexual differentiation of the rodent brain
What the sources say
- Partly supportedcites McCarthy & Arnold, 2011 sourceExperimental — accuracy not yet measured
The citation is attached to the first clause, about a female-like brain developing without perinatal testosterone, rather than to the later claim about testosterone treatment. The “Classic model: hormone-mediated organization/activation” section describes testosterone’s developmental masculinizing effects, but the “Parallel hormonal effects on diverse pathways and circuits” section says estradiol is required for normal female brain development. The source therefore does not support describing female brain development simply as a default program. (LLM, conf=0.80)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
In the paper
“elevated stress hormones can negatively regulate the reproductive neuroendocrine axis and consequently, the levels of circulating gonadal hormones”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Introduction
What the sources say
- Not checked — no full text of the sourcecites Rivier & Rivest, 1991 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The HPA axis influences many physiological functions making an organism’s response to changes in the environment appropriate for its reproductive status.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“crosstalk between the hypothalamic–pituitary–gonadal (HPG) and HPA axes could lead to abnormalities of stress responses.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Abstract
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“the acute activation of stress responses makes an individual more adaptable and allows one to cope with events that jeopardize homeostasis, whether real or perceived, by increasing awareness to our surroundings, and enhancing analgesia, cognition, and euphoria”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Introduction
What the sources say
- Not checked — no full text of the sourcecites Charmandari, Tsigos, & Chrousos, 2005 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In humans, a dysregulated stress response is one of the most common symptoms seen across many neuropsychiatric disorders”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Although the acute HPA response to stressors is a beneficial response”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“the estrogen receptors α and β have been reported to regulate the CRH-BP promoter in vitro, and estradiol has been shown to promote the induction of endogenous CRH-BP”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > The pituitary gland
What the sources say
- Not checked — no full text of the sourcecites van de Stolpe et al., 2004 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Both estrogen and testosterone have been shown to modulate the levels of CORT, and the degree to which activation of the HPA axis is driven is also influenced by both of these hormones, suggesting an interaction between the HPA and the HPG axes”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > The adrenal gland
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“CBG, or transcortin, is synthesized mainly by hepatocytes and binds CORT with high affinity to transport CORT in blood.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > The adrenal gland
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“the increase in Crh-BP mRNA levels observed following restraint stress is blunted by adrenalectomy, or depletion of endogenous glucocorticoids, indicating that glucocorticoids play a fundamental role in the regulation of CRH-BP”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > The pituitary gland
What the sources say
- Not checked — no full text of the sourcecites McClennen, Cortright, & Seasholtz, 1998 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“CORT increases following a stressor are higher and remain elevated for longer in female rats”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > The adrenal gland
What the sources say
- Not checked — no full text of the sourcecites Figueiredo, Dolgas, & Herman, 2002 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“it is possible that CRH-BP could be mediating the levels of CRH sensed by the pituitary gland through an ER-dependent mechanism, bringing CRH sensitivity back to homeostatic levels after stress.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > The pituitary gland
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“CBG also binds other hormones, including androgens and progesterone, which in humans are thought to displace cortisol from CBG”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > The adrenal gland
What the sources say
- Not checked — no full text of the sourcecites Dunn, Nisula, & Rodbard, 1981 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“CRH neurons in the rat PVN express estrogen receptor β, but not estrogen receptor α”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > The pituitary gland
What the sources say
- Not matchedcites Laflamme, Nappi, Drolet, Labrie, & Rivest, 1998
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites Mitra et al., 2003 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“On the other hand, it is thought that GRs likely become occupied following rises in CORT that can occur after activation of the HPA axis (Reul, van den Bosch, & de Kloet, 1987) and/or at peak concentrations achieved during the diurnal cycle.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > Negative feedback and corticosteroid receptors
What the sources say
- Not checked — no full text of the sourcecites Reul, van den Bosch, & de Kloet, 1987 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Gonadectomy of male rats elevates, while androgen replacement blunts the CORT and ACTH response to stress”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > The adrenal gland
What the sources say
- Not matchedcites Handa et al., 1994
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
None of the sources cited for this claim have been checked yet.
In the paper
“In a series of early studies, PVN infusion of glucocorticoids resulted in decreased activation of the HPA axis, suggesting that this brain nucleus is central to this adaptive process (Kovacs & Makara, 1988; Sawchenko, 1987).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > Negative feedback and corticosteroid receptors
What the sources say
- Not matchedcites Kovacs & Makara, 1988
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites Sawchenko, 1987 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“It is secreted by anterior pituitary corticotropes, and subsequently binds free CRH (Figure 1), thus preventing it from binding to its receptor and thereby blocking the actions of CRH on anterior pituitary corticotrophs”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > The pituitary gland
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Corticotrophs in the rat pituitary also express both estrogen receptor subtypes (α and β), but only a pituitary-specific truncated estrogen receptor product (TERP) mRNA transcript changes levels (4-to 7-fold increase) following estradiol treatment”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > The pituitary gland
What the sources say
- Not checked — no full text of the sourcecites Mitchner, Garlick, & Ben-Jonathan, 1998 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“AVP can be co-expressed with CRH in the rat PVN, and can be co-secreted with CRH where it acts at the pituitary to enhance the secretagouge activity of CRH (Rivier, Rivier, Mormede, & Vale, 1984; Rivier & Vale, 1983, 1985).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Gonadal hormones and neuropeptidergic regulation of the HPA > Steroid hormone control of arginine vasopressin and regulation of the HPA
What the sources say
- Not checked — no full text of the sourcecites Rivier, Rivier, Mormede, & Vale, 1984 source
- Not matchedcites Rivier & Vale, 1983, 1985
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, gonadal steroids are not only critical for the correct programing of the HPA axis during the perinatal period, but also play a role in establishing the HPA axis response to stress at puberty.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > Gonadal hormone fluctuations and the HPA axis
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The nanopeptide hormone, oxytocin, is primarily produced by neurons residing in the PVN and SON (Onaka, 2004).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Gonadal hormones and neuropeptidergic regulation of the HPA > Gonadal steroid effects on oxytocin and the HPA axis
What the sources say
- Not checked — no full text of the sourcecites Onaka, 2004 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“OT neurons in the PVN can also regulate the HPA axis since PVN OT is released into the hypothalamo-hypophyseal portal vasculature, enhancing the CRH-mediated release of ACTH via binding the V1b type vasopressin receptor (Schlosser, Almeida, Patchev, Yassouridis, & Elands, 1994).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Gonadal hormones and neuropeptidergic regulation of the HPA > Gonadal steroid effects on oxytocin and the HPA axis
What the sources say
- Not checked — no full text of the sourcecites Schlosser, Almeida, Patchev, Yassouridis, & Elands, 1994 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Interestingly, although pre-pubertal and adult male rats exhibit similar CORT and ACTH peak levels following acute stress, pre-pubertal animals take 30–45 min longer to return to baseline levels (Romeo et al., 2006; Romeo, Lee, & McEwen, 2004).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > Gonadal hormone fluctuations and the HPA axis
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This relationship challenges the experimental approach of using intact females in the study of the stress circuitry and indicates that estrous cyclicity should be monitored in order to allow interpretation of results from females.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The HPA axis – overview > Gonadal hormone fluctuations and the HPA axis
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“The nanopeptide, AVP, has been shown to be involved in the regulation of the stress response and circadian rhythms, as well as osmoregulation, paternal behaviors, and aggression (Sladek, 2010).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Gonadal hormones and neuropeptidergic regulation of the HPA > Steroid hormone control of arginine vasopressin and regulation of the HPA
What the sources say
- Not matchedcites Sladek, 2010
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Similarly, Crh promoter activity can be augmented by estradiol or the ERβ agonist, DPN, but not the ERα agonist, PPT (Ogura, Kageyama, Hanada, Kasckow, & Suda, 2008).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Gonadal hormones and neuropeptidergic regulation of the HPA > CRH regulation by estrogen and androgen receptors
What the sources say
- Not matchedcites Ogura, Kageyama, Hanada, Kasckow, & Suda, 2008
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“A relatively recent player implicated in the regulation of GnRH was introduced with the discovery of the RFamide, kisspeptin (Lee et al., 1996). Kisspeptin is a hypothalamic peptide encoded by the KiSS 1 gene (Kotani et al., 2001) and it has been found to be a potent stimulus for GnRH secretion (Herbison, 2016).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The hypothalamic–pituitary–gonadal axis > Steroid feedback loop
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“In rodents, estradiol is also known to have a stimulatory effect on GnRH secretion, and this positive feedback action is essential for ovulation in the female (Evans, Dahl, Mauger, & Karsch, 1995; Levine & Ramirez, 1980; Sarkar & Fink, 1980).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The hypothalamic–pituitary–gonadal axis > Steroid feedback loop
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Early studies failed to detect the presence of estrogen receptor in GnRH neurons, giving rise to the hypothesis that estrogen negative feedback was indirect, perhaps through estrogen receptors that were found in neighboring GABAergic neurons (Shivers, Harlan, Morrell, & Pfaff, 1983).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The hypothalamic–pituitary–gonadal axis > Steroid feedback loop
What the sources say
- Not checked — no full text of the sourcecites Shivers, Harlan, Morrell, & Pfaff, 1983 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Another twist on the potential mechanism for the HPA down-regulation by testosterone is through its conversion to 3β-diol, a weak androgen, which has been shown to bind ERβ [reviewed in Handa, Weiser, and Zuloaga (2009b)].”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Gonadal hormones and neuropeptidergic regulation of the HPA > Gonadal steroid effects on oxytocin and the HPA axis
What the sources say
- Not matchedcites Handa, Weiser, and Zuloaga (2009b)
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
None of the sources cited for this claim have been checked yet.
In the paper
“In the rodent, GnRH neurons are located in a swath from the medial septum to the medial pre-optic area, whereas in the human and non-human primate they are found further caudal in the medial basal hypothalamus (Rance, Young, & McMullen, 1994; Witkin, Paden, & Silverman, 1982).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The hypothalamic–pituitary–gonadal axis > Gonadotropin releasing hormone (GnRH)
What the sources say
- Not checked — no full text of the sourcecites Rance, Young, & McMullen, 1994 source
- Not matchedcites Witkin, Paden, & Silverman, 1982
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This long-loop negative feedback is similar to that of many neuroendocrine axes, where the end product, in this case, estradiol or testosterone, acts upon hypothalamic “motorneurons” that drive the neuroendocrine axis.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The hypothalamic–pituitary–gonadal axis > Steroid feedback loop
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“GnRH neurons have a very curious lifespan, arising in the nasal placode in early development and then migrating into the brain along the vomeronasal nerve to eventually take up their adult location in the hypothalamus (Schwanzel-Fukuda & Pfaff, 1989; Tobet & Schwarting, 2006; Wray, Nieburgs, & Elkabes, 1989).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The hypothalamic–pituitary–gonadal axis > Gonadotropin releasing hormone (GnRH)
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“GnRH neurons do not seem to express ERα either, suggesting that another upstream player is involved in the regulation of GnRH (Herbison & Theodosis, 1992).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The hypothalamic–pituitary–gonadal axis > Steroid feedback loop
What the sources say
- Not checked — no full text of the sourcecites Herbison & Theodosis, 1992 source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This relationship has been demonstrated numerous times by studies using castrated male rats, and other species, where castration results in increased levels of gonadotropins and testosterone replacement drives secretion back to baseline (Damassa, Kobashigawa, Smith, & Davidson, 1976; Tilbrook & Clarke, 1995).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The hypothalamic–pituitary–gonadal axis > LH and FSH action on steroidogenesis: males
What the sources say
- Not checked — no full text of the sourcecites Damassa, Kobashigawa, Smith, & Davidson, 1976 source
- Not matchedcites Tilbrook & Clarke, 1995
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Moreover, studies have demonstrated that slow release of GnRH can selectively drive the synthesis of FSH-β in the anterior pituitary gland, whereas fast pulses of GnRH selectively drive LH-β synthesis (Burger, Dalkin, Aylor, Haisenleder, & Marshall, 2002; Haisenleder, Dalkin, Ortolano, Marshall, & Shupnik, 1991; Kaiser, Jakubowiak, Steinberger, & Chin, 1997).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The hypothalamic–pituitary–gonadal axis > Gonadotropin releasing hormone (GnRH)
What the sources say
- Not matchedcites Burger, Dalkin, Aylor, Haisenleder, & Marshall, 2002
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites Haisenleder, Dalkin, Ortolano, Marshall, & Shupnik, 1991 source
- Not checked — no full text of the sourcecites Kaiser, Jakubowiak, Steinberger, & Chin, 1997 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“This positive feedback response is a sexually differentiated phenomenon, where male rodents are incapable of responding to elevated estradiol with a surge of LH (Corbier, 1985; Gogan, Beattie, Hery, Laplante, & Kordon, 1980; Olster & Blaustein, 1991).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The hypothalamic–pituitary–gonadal axis > Steroid feedback loop
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, testosterone can be further converted into 3β-diol and thereby act through ERβ to reduce the gain of the HPA axis (Figure 3).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Steroid metabolites and the control of the HPA axis
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, it appears to be the interaction of these three players that sculpt the pulsatile patterns of GnRH secretion. While kisspeptin and neurokinin B can increase the frequency of GnRH pulses, secretion of dynorphin will reduce pulse frequency.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The hypothalamic–pituitary–gonadal axis > Steroid feedback loop
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Neurokinin B and kisspeptin stimulate GnRH release and co-localize in some arcuate nucleus neurons.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“As discussed here, internal cues are critical for the regulation of the HPG axis. However, external signals, like stress, are well known to affect this axis also.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Steroid metabolites and the control of the HPA axis
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Peripheral steroid hormones are able to cross the brain-blood barrier, due to their lipophilic nature, and can be converted to biologically active metabolites within the brain through actions of several enzymes such as aromatase, 3β-HSD, and 5α-reductase (Lephart, Lund, & Horvath, 2001).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Steroid metabolites and the control of the HPA axis
What the sources say
- Not checked — no full text of the sourcecites Lephart, Lund, & Horvath, 2001 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Since ERs can have opposing effects on HPA activity (ERβ decreases, while ERα increases HPA axis gain), then the gain of the HPA axis in males could be dependent upon the enzymes levels that are present.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Steroid metabolites and the control of the HPA axis
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: ERβ decreases HPA axis gain while ERα increases it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, additional regulation could be provided by two other factors. First, the quantity of ERs present in a particular brain region, and, second, the ratio of ERα vs. ERβ at a particular time point.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Steroid metabolites and the control of the HPA axis
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The first observations indicating that kisspeptin neurons might be involved in the negative feedback regulation by gonadal steroids were seen in gonadectomized rats, where removal of the gonads significantly increased KiSS 1 mRNA levels, and this effect was reversed by replacement with gonadal steroids (Navarro et al., 2004).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The hypothalamic–pituitary–gonadal axis > Steroid feedback loop
What the sources say
- Not checked — no full text of the sourcecites Navarro et al., 2004 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“For instance, basal and stress-induced CORT have been shown to be greater in female than in male rodents (Critchlow, Liebelt, Bar-Sela, Mountcastle, & Lipscomb, 1963; Handa, Burgess, Kerr, & O’Keefe, 1994; Kitay, 1961).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Sexual differentiation of the HPA axis
What the sources say
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Moreover, sex differences in the pulsatile pattern of CORT secretion have been identified by the Lightman group, where females have a higher amplitude and frequency of CORT pulses than males (Lightman & Conway-Campbell, 2010).”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Sexual differentiation of the HPA axis
What the sources say
- Not checked — no full text of the sourcecites Lightman & Conway-Campbell, 2010 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Correspondingly, if testosterone is converted into estradiol, both ERs could be activated due to the indiscriminative binding properties of estradiol to both ERs.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Steroid metabolites and the control of the HPA axis
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Rising titers of estradiol can activate kisspeptin neurons in the AVPV causing a concomitant activation of GnRH neurons, which apparently drives the pre-ovulatory surge of GnRH from the hypothalamus.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > The hypothalamic–pituitary–gonadal axis > Steroid feedback loop
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The fluctuations in estradiol and progesterone present across the estrous cycle of adult rodents are arguably responsible for most activational effects in the female brain, thereby regulating the behavioral and physiological repertoire to stress seen during adulthood.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Summary and conclusion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the localization, expression levels, and activity of steroid hormone receptors may further help explain why certain hormones and their metabolites have sex-specific effects.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Summary and conclusion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“To maintain homeostasis, the neuroendocrine system continuously monitors the levels of gonadal steroids using estrogen and androgen receptors found in the hypothalamus.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Summary and conclusion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In sum, the HPG and HPA axes work in a parallel, and in a carefully choreographed fashion, to successfully maintain species survival and perhaps minimize allostatic”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Summary and conclusion
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“It is now known that hormones have specific actions in given brain regions.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Summary and conclusion
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The HPG and HPA axes both exhibit striking sex differences, which are organized and activated by dynamic changes in sex and stress hormones across the lifespan.”
§ Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity > Summary and conclusion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
The paper relies on this without support.
The basis for sex differences in stress coping is unknown, partly because early research used male rodents.
“The basis for these differences is unknown, in part because much of the early work in this field was performed on male rodents”
The paper relies on this without support.
Gonadal steroids are largely responsible for sex differences in response to physical or psychological threats.
“Gonadal steroids are largely responsible for the differential response to physical or psychological threats between sexes.”
The paper relies on this without support.
ERβ decreases HPA axis gain while ERα increases it.
“Since ERs can have opposing effects on HPA activity (ERβ decreases, while ERα increases HPA axis gain)”
The paper relies on this without support.
Neurokinin B and kisspeptin stimulate GnRH release and co-localize in some arcuate nucleus neurons.
“Both, neurokinin B and kisspeptin, have now been shown to have stimulatory effects on the release of GnRH and are both co-localized in some neurons of the arcuate nucleus.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Repression of the HPA axis is due to inhibitory activities exerted by estrogens, androgens, progesterone, and their metabolites on neurons of the hypothalamic peri-paraventricular and paraventricular nuclei, and the anterior pituitary.”
From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [72]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Such double-inhibitory loop operates physiological functions [72,131], but under peculiar circumstances could lead to functional disorders.”
From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [72]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Differential stress-related phenotypes between males and females are also related to the gonadal hormones, which play important roles in the establishment, activation and regulation of the HPA axis (276).”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [276]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Repression of the HPG axis is due to inhibitory activities exerted by corticosteroids on hypothalamic kisspeptin and gonadotropin-releasing-hormone (GnRH) neurons, the anterior pituitary, and gonads [72].”
From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [72]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“salivary cortisol level reaches its maximum about 20 minutes after acute stress reaction (Fan et al., 2009;Oyola & handa, 2017).”
From Salivary testosterone and cortisol response in acute stress modulated by seven sessions of mindfulness meditation in young males (2024) · cites this paper as Oyola & handa, 2017
Experimental — accuracy not yet measured
Citations
Cites
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The Grandmother Hypothesis: A perspective from cardiovascular aging
Zhang, W. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103334
Acute stress modulates flavour neophobia as a function of sex and palatability in ratsPreprint
la Casa, L. G. D., Cintado, M. Á., García-Gálvez, R. A., Gómez‐Álvarez, M., & Santos‐Carrasco, D. (2026) · SSRN Electronic Journal · doi:10.2139/ssrn.7352100
Corrêa, M. D. S., Lopes, L. V., dos Santos, A. C. Q., Castro, J. C., Lourenço, W. T. B., Silva, A. C. D. C., Ferreira, T. L., Tiba, P. A., & Fornari, R. V. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.08.21.745892
Multilevel sex-influenced neurobiological signatures of early life adversity
Narayan, S. V., Beer, C., Kovářová, V., Castoldi, C., Štark, T., Bianco, B. D., Röh, S., Sauer, S., Bordes, J., Karamihalev, S., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2603982123 · Cited by 1
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Sex Differences in Major Depressive Disorder
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Major Depressive Disorder and Infertility
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Metadata
- Authors
- Oyola, M. G., & Handa, R. J.
- Affiliations
- Colorado State University (US)
- Corresponding author
- Oyola, Mario G.
- Venue
- Stress
- Publisher
- Informa UK Limited
- Published
- 2017-08-31
- Volume
- 20
- Issue
- 5
- Pages
- 476-494
- ISSN
- 1025-3890 (ISSN-L)
- 1607-8888
- PMC
- PMC5815295
- OpenAlex
- W2751431338
- Semantic Scholar
- b17ba8760d06e7eacd14a73ef5cc58a5e8851938
- Cited by
- 710
- References
- 233
- Citations by year
- 2026: 86 · 2025: 101 · 2024: 91 · 2023: 103 · 2022: 98 · 2021: 108 · 2020: 62 · 2019: 41 · 2018: 19 · 2017: 1
- FWCI
- 2.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Stress (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (RO1DK105826)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-gonadal axis, sex differences, stress responsivity, sex steroids, estradiol, estrous cycle, HPA axis dysregulation, organizational effects, chronic stress, neuropsychiatric disorders
- MeSH terms
- Animals, Female, Gonads, Humans, Hypothalamo-Hypophyseal System, Male, Pituitary-Adrenal System, Sex Characteristics, Sex Factors, Gonadal Steroid Hormones, Stress, Psychological, Estrous Cycle, Mice, Rats
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