The DOI matches its Crossref record; 203 of the 205 references it cites were found in a registry or an index; 3 of the 145 sources its claims cite were checked for support.
Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes
Open accessAbstract
Despite affecting millions of individuals, the etiology of hot flushes remains unknown. Here we review the physiology of hot flushes, CNS pathways regulating heat-dissipation effectors, and effects of estrogen on thermoregulation in animal models. Based on the marked changes in hypothalamic kisspeptin, neurokinin B and dynorphin (KNDy) neurons in postmenopausal women, we hypothesize that KNDy neurons play a role in the mechanism of flushes. In the rat, KNDy neurons project to preoptic thermoregulatory areas that express the neurokinin 3 receptor (NK3R), the primary receptor for NKB. Furthermore, activation of NK3R in the median preoptic nucleus, part of the heat-defense pathway, reduces body temperature. Finally, ablation of KNDy neurons reduces cutaneous vasodilatation and partially blocks the effects of estrogen on thermoregulation. These data suggest that arcuate KNDy neurons relay estrogen signals to preoptic structures regulating heat-dissipation effectors, supporting the hypothesis that KNDy neurons participate in the generation of flushes.
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Written from the paper’s full text.
TL;DR
This review proposes that hypothalamic KNDy (kisspeptin/neurokinin B/dynorphin) neurons relay estrogen-withdrawal signals to preoptic thermoregulatory pathways and thereby contribute to hot flushes. Evidence from postmenopausal women and rat models links KNDy/NK3R signaling to LH pulses, cutaneous vasodilatation, and body temperature control.
Key findings
- In postmenopausal women, infundibular (arcuate) neurons expressing estrogen receptor, kisspeptin, and NKB are hypertrophied, with increased NKB and kisspeptin gene expression; dynorphin neurons are enlarged but dynorphin mRNA-expressing neuron number is reduced. Ovariectomy induces and estrogen reverses these changes in monkeys.
- Rat KNDy neurons project to preoptic thermoregulatory areas, including the median preoptic nucleus (MnPO), which expresses NK3R. Microinfusion of the NK3R agonist senktide (90 pmol) into the MnPO reduced body temperature by about 1.5 °C.
- KNDy neuron ablation with NK3-SAP destroyed nearly all arcuate kisspeptin- and NKB-immunoreactive neurons and reduced arcuate dynorphin neurons by 76%. Ablated rats did not show the post-ovariectomy LH increase, had lower tail skin temperatures, better defended core temperature against heat, and did not respond to estrogen with reduced core temperature.
- Ovariectomized rats without estrogen showed a thermoneutral zone shifted to lower ambient temperatures, with the skin vasodilatation threshold 4 °C lower than in estrogen-treated rats. Estrogen reduced dark-phase tail skin temperature by >3 °C, and a small core temperature rise preceded 65%–76% of hot flushes in women.
Methods
- Narrative review and hypothesis paper synthesizing human postmortem hypothalamic studies, ovariectomy/estrogen-replacement studies in monkeys and rats, and the authors’ rat thermoregulation experiments.
- Data include postmortem hypothalamic tissue from premenopausal and postmenopausal women; ovariectomized monkeys and rats with estrogen replacement; rat tail skin and core temperature recordings; Fos immunocytochemistry; anterograde tract-tracing; NK3R agonist microinfusion; and NK3-SAP ablation.
- Main analysis is qualitative integration of anatomic, neuroendocrine, and thermoregulatory findings to support a KNDy-neuron mechanism for hot flushes.
Limitations
- Stated: whether rats actually experience hot flushes after estrogen withdrawal is unknown; rats cannot report flush onset, so studies rely on objective measures such as tail skin temperature.
- Stated: normal female rats show wide tail skin temperature fluctuations, and objective measures in women may reflect physiological events other than flushes; concordance between self-reported flushes and skin conductance can be limited.
- Evident: the central hypothesis is largely indirect and not directly tested in humans; much of the causal evidence comes from rat models, and the review notes that roles for other KNDy peptides, substance P, or GnRH neurons remain to be explored.
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Claims the paper makes
82 Not checked yet · 18 Own interpretation · 6 No basis given · 5 Own result · 2 Partly supported · 1 Supported so far · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Autonomic thermoeffectors are controlled by neural pathways passing through the preoptic anterior hypothalamus, specifically, through the MnPO and the medial preoptic area (Boulant, 2000; Romanovsky et al., 2009).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 4. CNS pathways controlling heat dissipation effectors > 4.3. Hypothalamic and downstream neural pathways for thermoregulation
What the sources say
- Not checked yetcites Boulant, 2000 source
- Partly supportedcites Romanovsky et al., 2009 sourceExperimental — accuracy not yet measured
The sections on afferent and efferent pathways describe thermoeffector control through the MnPO and medial preoptic area (MPO), and say that efferent pathways to all autonomic thermoeffectors include MPO neurons. But the MnPO-to-MPO route is presented as a model for cutaneous warming; the paper hypothesizes that pathways carrying visceral TRPV1 signals to autonomic thermoeffectors do not involve the MnPO. The claim is therefore too broad in implying that these pathways all pass through both areas. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
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The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Conversely, blocking transmission through the MnPO blocks the stimulatory effects of skin warming on cutaneous vasodilatation (Nakamura and Morrison, 2008, 2010; Romanovsky et al., 2009).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 4. CNS pathways controlling heat dissipation effectors > 4.3. Hypothalamic and downstream neural pathways for thermoregulation
What the sources say
- Not checked yetcites Nakamura and Morrison, 2008
- Not checked yetcites Nakamura and Morrison, 2010
- Partly supportedcites Romanovsky et al., 2009 sourceExperimental — accuracy not yet measured
In “Afferent Pathways That Control Autonomic Thermoeffectors” (page unavailable), the paper models skin-warming signals as passing through the MnPO to neurons controlling skin vasomotor tone. But it says the MnPO connection was a hypothesis being tested; the reported blockade experiment targeted the MPO, not the MnPO. It therefore does not establish that blocking transmission through the MnPO blocks warming-induced cutaneous vasodilatation. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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
“Our prediction that KNDy neurons project to preoptic regions that control heat dissipation effectors was correct, as demonstrated by KNDy neuron projections to the MnPO and medial preoptic area (Krajewski et al., 2010; Yeo and Herbison, 2011).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 6. Evidence that KNDy neurons modulate LH secretion and body temperature in the rat > 6.1. KNDy neurons project to thermoregulatory structures (MnPO, medial preoptic area) and GnRH axons in the median eminence
What the sources say
- Supportedcites Krajewski et al., 2010 source
The Discussion identifies projections of arcuate NKB/kisspeptin/dynorphin neurons to the median preoptic nucleus (MnPO) and separately states that arcuate NKB neurons project to the medial preoptic area. The supplied passages do not provide page numbers. (LLM, conf=0.94)
- Not checked yetcites Yeo and Herbison, 2011
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
In the paper
“Stereological analysis revealed no neuronal cell loss in the infundibular nucleus of post-menopausal women (Abel and Rance, 2000).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 3. Changes in KNDy neuron morphology and neuropeptide gene expression in the hypothalamus of postmenopausal women
What the sources say
- Not checked yetcites Abel and Rance, 2000
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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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 the rat, KNDy neurons project to preoptic thermoregulatory areas that express the neurokinin 3 receptor (NK3R), the primary receptor for NKB.”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
“Furthermore, activation of NK3R in the median preoptic nucleus, part of the heat-defense pathway, reduces body temperature.”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In addition, senktide markedly increased the number of Fos-ir nuclei in the MnPO, with minimal effects on adjacent nuclei (Dacks et al., 2011a).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 6. Evidence that KNDy neurons modulate LH secretion and body temperature in the rat > 6.2. Activation of NK3R in the MnPO lowers body temperature in the rat
What the sources say
- Not checked yetcites Dacks et al., 2011a
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Remarkably, the ambient temperature threshold for skin vasodilatation was 4 °C lower in ovariectomized rats, compared to ovariectomized rats receiving estrogen (Dacks and Rance, 2010).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 5. Effects of estrogen on hypothalamic thermoregulation in the rat > 5.2. Effects of estrogen on core temperature, the thermoneutral zone and hypothalamic Fos activation
What the sources say
- Not checked yetcites Dacks and Rance, 2010
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Using this paradigm, ovariectomized rats without estrogen replacement showed a shift in the thermoneutral zone to lower ambient temperatures (Fig. 8) (Dacks and Rance, 2010).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 5. Effects of estrogen on hypothalamic thermoregulation in the rat > 5.2. Effects of estrogen on core temperature, the thermoneutral zone and hypothalamic Fos activation
What the sources say
- Not checked yetcites Dacks and Rance, 2010
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — 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, at the ambient temperature of 24 °C, estrogen treatment of ovariectomized rats decreased the Fos expression in the MnPO, in parallel with the reduction in tail skin temperature.”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 5. Effects of estrogen on hypothalamic thermoregulation in the rat > 5.2. Effects of estrogen on core temperature, the thermoneutral zone and hypothalamic Fos activation
plaindirect- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 30
- Probably not a substantial claim. 21
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
“Finally, ablation of KNDy neurons reduces cutaneous vasodilatation and partially blocks the effects of estrogen on thermoregulation.”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Interestingly, on proestrous night (when endogenous estrogen levels are high), the average tail skin temperature was significantly decreased, with decreased variability (Fig. 7).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 5. Effects of estrogen on hypothalamic thermoregulation in the rat > 5.1. Effects of estrogen on tail skin temperature
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- 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 result the paper reports from its own data — 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 our study, however, at the neutral ambient temperature of 29.0 °C, vasoconstriction occurred in vehicle-infused animals, but not in rats in which senktide was microinfused in the MnPO.”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 6. Evidence that KNDy neurons modulate LH secretion and body temperature in the rat > 6.2. Activation of NK3R in the MnPO lowers body temperature in the rat
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — 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 contrast, the dark phase reduction in tail skin temperature by estrogen is large (>3 °C) and consistent (Fig. 7).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 5. Effects of estrogen on hypothalamic thermoregulation in the rat > 5.1. Effects of estrogen on tail skin temperature
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — 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 contrast, LH did not significantly increase after ovariectomy in KNDy ablated rats, and their serum LH was lower regardless of estrogen replacement.”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 6. Evidence that KNDy neurons modulate LH secretion and body temperature in the rat > 6.3. Effects of KNDy neuron ablation on the estrogen modulation of LH secretion and thermoregulation
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Moreover, KNDy-ablated rats were able to better defend their core temperatures against heat than control rats, and unlike controls, did not respond to estrogen treatment with a reduction in core temperature.”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 6. Evidence that KNDy neurons modulate LH secretion and body temperature in the rat > 6.3. Effects of KNDy neuron ablation on the estrogen modulation of LH secretion and thermoregulation
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Remarkably, KNDy neuron ablation consistently reduced tail skin temperatures, indicating that KNDy neurons facilitate cutaneous vasodilatation (Fig. 12) (Mittelman-Smith et al., 2012a).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 6. Evidence that KNDy neurons modulate LH secretion and body temperature in the rat > 6.3. Effects of KNDy neuron ablation on the estrogen modulation of LH secretion and thermoregulation
What the sources say
- Not checked yetcites Mittelman-Smith et al., 2012a
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Dynorphin neurons are also enlarged in the infundibular nucleus of postmenopausal women, but the number of dynorphin mRNA-expressing neurons is reduced (Rometo and Rance, 2008).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 1. Introduction
What the sources say
- Not checked yetcites Rometo and Rance, 2008
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“These neurons express estrogen receptor, kisspeptin and neurokinin B (NKB) and the cellular hypertrophy is accompanied by increased neurokinin B and kisspeptin gene expression (Fig. 1) (Rance et al., 1990; Rance and Young, 1991; Rometo et al., 2007).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 1. Introduction
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“The most effective treatment of hot flushes is estrogen replacement therapy, but the Women’s Health Initiative Study raised questions about the long-term safety of this treatment (Rossouw et al., 2002).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 1. Introduction
What the sources say
- Not checked yetcites Rossouw et al., 2002 source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The hypertrophy and increased kisspeptin and NKB gene expression in postmenopausal women are secondary to estrogen withdrawal, because these changes are induced by ovariectomy (Fig. 2) and reversed by estrogen replacement of young cynomolgus monkeys (Abel et al., 1999; Rometo et al., 2007; Sandoval-Guzmán et al., 2004).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 1. Introduction
What the sources say
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.
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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
“In the majority of menopausal women, estrogen withdrawal causes hot flushes (also known as hot flashes), a disorder of hypothalamic thermoregulation.”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 1. Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
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- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Moreover, two of the peptides in the hypertrophied neurons, kisspeptin and neurokinin B, are essential for pubertal development and fertility in the human (Chan et al., 2011; Topaloglu et al., 2009, 2012).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 1. Introduction
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. It may state two separate claims as one.
In the paper
“Despite affecting millions of individuals, the etiology of hot flushes remains unknown.”
- Also stated in: § 1. Introduction · plain
“Despite the millions of individuals affected, there has been limited basic research on the physiology of hot flushes and their etiology has remained an enigma (Kronenberg, 2010).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > Abstract
What the sources say
- Not checked yetcites Kronenberg, 2010 source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
- Also stated in: § 1. Introduction · plain
In the paper
“Eventually, most (but not all) postmenopausal women will acclimate to the low estrogen level, and the flushes will disappear (Kronenberg, 1990).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 2. Physiology of hot flushes
What the sources say
- Not checked yetcites Kronenberg, 1990 source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Withdrawal of gonadal steroids induces flushes in a variety of patients: women treated with tamoxifen for breast cancer, women with premature ovarian failure, aging men with diminished testosterone, and men with prostate carcinoma undergoing androgen ablation therapy (Santoro, 2008).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 2. Physiology of hot flushes
What the sources say
- Not checked yetcites Santoro, 2008 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Because KNDy neurons have been identified in multiple experimental animals, information on the role of these neurons in LH secretion is accumulating at a rapid pace (Kinsey-Jones et al., 2012; Lehman et al., 2010; Mittelman-Smith et al., 2012b; Rance et al., 2010; Wakabayashi et al., 2010).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 1. Introduction
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Hot flushes are characterized by a transient and intense sensation of heat accompanied by the activation of heat-loss effectors including skin vasodilatation, sweating, and cold-seeking behavior (Fig. 3) (Freedman, 2001; Kronenberg, 2010).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 2. Physiology of hot flushes
What the sources say
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: 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.
None of the sources cited for this claim have been checked yet.
In the paper
“It is not the absolute level of estrogens, but the rate of estrogen withdrawal that determines the onset of flushes (Kronenberg, 2010; Santoro, 2008).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 2. Physiology of hot flushes
What the sources say
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.
Probably not a substantial claim.
In the paper
“Flushes often begin during the perimenopausal period when there are wide fluctuations in serum estrogen (Burger et al., 2002).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 2. Physiology of hot flushes
What the sources say
- Not checked yetcites Burger et al., 2002 source
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: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Complete coexpression of kisspeptin, NKB and dynorphin is not always found (Hrabovszky et al., 2012; Navarro et al., 2011), but this issue is complicated by limitations in the sensitivity of detection (Ruka et al., 2013) and differential expression depending on developmental stage (Gill et al., 2012) or physiological state of the animal (Foradori et al., 2005; Navarro et al., 2011; Rance and Bruce”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 1. Introduction
What the sources say
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.
None of the sources cited for this claim have been checked yet.
In the paper
“We hypothesized that KNDy neurons could contribute to the generation of flushes (Rance and Young, 1991) because estrogen withdrawal leads to such remarkable changes in cell size and gene expression in the hypothalamus of postmenopausal women (Abel et al., 1999; Rance and Young, 1991; Rometo et al., 2007; Sandoval-Guzmán et al., 2004).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 1. Introduction
What the sources say
- Not checked yetcites Rance and Young, 1991
- Not checked yetcites Abel et al., 1999
- Not checked yetcites Rometo et al., 2007 source
hedgedconditional- Asserted: fails — The authors may not 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 authors may not put it forward as true.
In the paper
“Hot flushes occur in response to ovariectomy in young women and are effectively treated by estrogen replacement (Santoro, 2008).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 2. Physiology of hot flushes
What the sources say
- Not checked yetcites Santoro, 2008 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
“Similarly, GnRH does not cause the flushes, as estrogen withdrawal produces hot flushes in women who lack hypothalamic GnRH neurons due to Kallman’s syndrome (Gambone et al., 1984; Schwanzel-Fukuda et al., 1989).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 2. Physiology of hot flushes
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Hot flushes can be triggered by a variety of stimuli including thermal (increased ambient temperature or hot beverages), chemical (caffeine or spicy food) or other (stress or anxiety) (Archer et al., 2011; Freedman, 2001).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 2. Physiology of hot flushes
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
“However, even in these women, hot flushes may reoccur if estrogens are administered and then withdrawn (Jensen and Christiansen, 1983).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 2. Physiology of hot flushes
What the sources say
- Not checked yetcites Jensen and Christiansen, 1983
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.
None of the sources cited for this claim have been checked yet.
In the paper
“In parallel to the findings in postmenopausal women, ovariectomy decreased dynorphin gene expression in the arcuate nucleus of the ewe (Foradori et al., 2005), but ovariectomized mice exhibited increased dynorphin mRNA, compared to estrogen treated mice (Navarro et al., 2009).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 3. Changes in KNDy neuron morphology and neuropeptide gene expression in the hypothalamus of postmenopausal women
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
“The preoptic warm-sensitive neurons are GABAergic (Eberwine and Bartfai, 2011), and activation of these neurons inhibits the rostral raphe pallidus, resulting in cutaneous vasodilatation.”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 4. CNS pathways controlling heat dissipation effectors > 4.3. Hypothalamic and downstream neural pathways for thermoregulation
What the sources say
- Not checked yetcites Eberwine and Bartfai, 2011
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Emerging evidence that KNDy neurons are an important part of the GnRH pulse generator (Lehman et al., 2010; Rance et al., 2010; Wakabayashi et al., 2010) strongly supports the hypothesis that they could also be involved in the generation of flushes.”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 2. Physiology of hot flushes
What the sources say
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.
None of the sources cited for this claim have been checked yet.
In the paper
“The significance of this line of inquiry became apparent with the discovery that individuals with mutations in the genes encoding NKB or its receptor (NK3R) are infertile and do not transition through puberty (Gianetti et al., 2010; Topaloglu et al., 2009; Young et al., 2010).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 3. Changes in KNDy neuron morphology and neuropeptide gene expression in the hypothalamus of postmenopausal women
What the sources say
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Thermosensitive neurons also receive information related to blood pressure, osmolarity, pyrogens, glucose concentration, and gonadal hormones, including estrogen (Boulant, 2000; Silva and Boulant, 1986).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 4. CNS pathways controlling heat dissipation effectors > 4.1. Thermosensors
What the sources say
- Not checked yetcites Boulant, 2000 source
- Not checked yetcites Silva and Boulant, 1986
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: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on 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
“Thus, convergence of information on warm-sensitive neurons provides a mechanism to modulate the activation of thermoregulatory effectors, based on the physiological state of the animal.”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 4. CNS pathways controlling heat dissipation effectors > 4.1. Thermosensors
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 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
“Based on the marked changes in hypothalamic kisspeptin, neurokinin B and dynorphin (KNDy) neurons in postmenopausal women, we hypothesize that KNDy neurons play a role in the mechanism of flushes.”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > Abstract
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.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Finally, lesions that include the MnPO result in hyperthermia, supporting a role for this nucleus in the control of heat-defense effectors (Almeida et al., 2006b; Romanovsky et al., 2003; Yoshida et al., 2009).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 4. CNS pathways controlling heat dissipation effectors > 4.3. Hypothalamic and downstream neural pathways for thermoregulation
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
“Excitation of the heat-defense pathway by skin warming inhibits the activity of sympathetic vasoconstrictor neurons, resulting in tail skin vasodilatation (Nakamura and Morrison, 2010).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 4. CNS pathways controlling heat dissipation effectors > 4.3. Hypothalamic and downstream neural pathways for thermoregulation
What the sources say
- Not checked yetcites Nakamura and Morrison, 2010
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Tail skin temperature is increased by ovariectomy (Berendsen et al., 2001; Kobayashi et al., 1995; Opas et al., 2004) and reduced by estrogen treatment of ovariectomized rats (Berendsen et al., 2001; Bowe et al., 2006; Dacks and Rance, 2010; Hosono et al., 2001; Kobayashi et al., 1995).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 5. Effects of estrogen on hypothalamic thermoregulation in the rat > 5.1. Effects of estrogen on tail skin temperature
What the sources say
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Thermosensitive neurons that do participate in physiological thermoregulation are predominantly warm-sensitive cells located mostly in the preoptic hypothalamus (Boulant, 2000; Nakayama et al., 1961).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 4. CNS pathways controlling heat dissipation effectors > 4.1. Thermosensors
What the sources say
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.
In the paper
“Therefore, the thermoneutral zone for the same animal varies widely, depending on the experimental setup (Romanovsky et al., 2002).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 4. CNS pathways controlling heat dissipation effectors > 4.2. The thermoneutral zone and thermoregulatory effectors
What the sources say
- Not checked yetcites Romanovsky et al., 2002 source
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: 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
“Thus, similar to postmenopausal women (Tankersley et al., 1992), estrogen replacement of ovariectomized rats improves the maintenance of core temperature during heat stress.”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 5. Effects of estrogen on hypothalamic thermoregulation in the rat > 5.2. Effects of estrogen on core temperature, the thermoneutral zone and hypothalamic Fos activation
What the sources say
- Not checked yetcites Tankersley et al., 1992 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Core temperature has been reported to be increased (Hosono et al., 1997a; Marrone et al., 1976), decreased (Wilkinson et al., 1980) or unaffected by estrogen treatment of ovariectomized rats (Hosono et al., 2001; Laudenslager et al., 1980; Williams et al., 2010).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 5. Effects of estrogen on hypothalamic thermoregulation in the rat > 5.2. Effects of estrogen on core temperature, the thermoneutral zone and hypothalamic Fos activation
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
“Because vasodilatation in the rat is accomplished by inhibiting vasoconstriction (O’Leary et al., 1985), these data show a vasodilator effect of NK3R MnPO neuron activation in neutral ambient temperatures, that is suppressed in the subneutral environment.”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 6. Evidence that KNDy neurons modulate LH secretion and body temperature in the rat > 6.2. Activation of NK3R in the MnPO lowers body temperature in the rat
What the sources say
- Not checked yetcites O’Leary et al., 1985 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.
In the paper
“These data provide evidence that the reduction in tail skin temperature by estrogen is part of the normal estrous cycle and physiologically relevant (Williams et al., 2010).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 5. Effects of estrogen on hypothalamic thermoregulation in the rat > 5.1. Effects of estrogen on tail skin temperature
What the sources say
- Not checked yetcites Williams et al., 2010 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.
In the paper
“In guinea pigs, core temperature is increased by ovariectomy and reduced by treatment with estrogen or a ligand for a membrane-associated estrogen receptor (Roepke et al., 2010).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 5. Effects of estrogen on hypothalamic thermoregulation in the rat > 5.2. Effects of estrogen on core temperature, the thermoneutral zone and hypothalamic Fos activation
What the sources say
- Not checked yetcites Roepke et al., 2010 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 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
“Therefore, NKB signaling (from KNDy neurons) could influence heat-defense effectors through projections to NK3R-expressing MnPO neurons or NK3R-expressing warm-sensitive neurons in the medial preoptic area.”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 6. Evidence that KNDy neurons modulate LH secretion and body temperature in the rat > 6.1. KNDy neurons project to thermoregulatory structures (MnPO, medial preoptic area) and GnRH axons in the median eminence
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
“KNDy neurons may play a role in this pathway because estrogen strongly suppresses kisspeptin and neurokinin B gene expression, as well as LH pulses and flushes.”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 6. Evidence that KNDy neurons modulate LH secretion and body temperature in the rat > 6.1. KNDy neurons project to thermoregulatory structures (MnPO, medial preoptic area) and GnRH axons in the median eminence
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. It may state two separate claims as one.
In the paper
“These data provide the first evidence that KNDy neurons promote cutaneous vasodilatation and participate in estrogen modulation of body temperature in the rat (Mittelman-Smith et al., 2012a).”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 6. Evidence that KNDy neurons modulate LH secretion and body temperature in the rat > 6.3. Effects of KNDy neuron ablation on the estrogen modulation of LH secretion and thermoregulation
What the sources say
- Not checked yetcites Mittelman-Smith et al., 2012a
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.
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 this review, we summarize the evidence gained in a rat model that estrogen-responsive KNDy neurons play a role in body temperature regulation and may activate thermoregulatory vasodilatation through projections to preoptic regions expressing NK3R.”
§ Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes > 7. Conclusions
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.
The paper relies on this without support.
There was virtually no information on the role of KNDy neurons in thermoregulation in any species before the authors' studies.
“There was, however virtually no information on the role of KNDy neurons in thermoregulation in any species.”
The paper relies on this without support.
Findings about KNDy neurons and thermoregulation in the rat are relevant to the mechanism of hot flushes in women.
“To address this issue, we established methods in our laboratory to examine how estrogen modulates thermoregulation and related neural pathways in the rat (Dacks et al., 2011b; Dacks and Rance, 2010; Williams et al., 2010).”
The paper relies on this without support.
Hot flushes are a manifestation of a central (hypothalamic) disorder of thermoregulation.
“One of the most prominent symptoms of menopause is the hot flush, a manifestation of a central (hypothalamic) disorder of thermoregulation.”
The paper relies on this without support.
Cutaneous vasodilatation is a cardinal sign of a hot flush.
“Because cutaneous vasodilatation is a cardinal sign of a hot flush, these data support the hypothesis that KNDy neurons could play a role in the generation of flushes.”
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 cited source says what the claim attributes to it.
In the citing paper
“There is growing evidence from Rance and colleagues [169] showing that estradiol can also affect central thermoregulatory pathways via actions on a group of estrogen-sensitive arcuate neurons that co-express kisspeptin, neurokinin B, and dynorphin (KNDy neurons) involved in the regulation of GnRH secretion.”
From Temperature regulation in women: Effects of the menstrual cycle (2020) · cites this paper as [169]
In the citing paper
“There is considerable interest in this group of neurons because they are thought to be involved in triggering hot flashes in peri- and post-menopausal women: KNDy neurons are hypertrophied post-menopause after estrogen withdrawal and ablation of these neurons reduces cutaneous vasodilatation and partially blocks the effects of estrogen on thermoregulation [169].”
From Temperature regulation in women: Effects of the menstrual cycle (2020) · cites this paper as [169]
In the citing paper
“There is considerable interest in this group of neurons because they are thought to be involved in triggering hot flashes in peri- and post-menopausal women: KNDy neurons are hypertrophied post-menopause after estrogen withdrawal and ablation of these neurons reduces cutaneous vasodilatation and partially blocks the effects of estrogen on thermoregulation [169].”
From Temperature regulation in women: Effects of the menstrual cycle (2020) · cites this paper as [169]
In the citing paper
“There is considerable interest in this group of neurons because they are thought to be involved in triggering hot flashes in peri- and post-menopausal women: KNDy neurons are hypertrophied post-menopause after estrogen withdrawal and ablation of these neurons reduces cutaneous vasodilatation and partially blocks the effects of estrogen on thermoregulation [169].”
From Temperature regulation in women: Effects of the menstrual cycle (2020) · cites this paper as [169]
In the citing paper
“Several physiological systems exhibit ultradian rhythms (URs) in the 1–3 h range, including the HPG axis60–65, the HPA axis66–72, and the suprachiasmatic nucleus73, 74 – the principal orchestrating brain area for circadian rhythms.”
From Maternal and Early-Life Circadian Disruption Have Long-Lasting Negative Consequences on Offspring Development and Adult Behavior in Mice (2017) · cites this paper as [63]
Citations
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How do you feel? Interoception: The sense of the physiological condition of the body
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The GPR54 Gene as a Regulator of Puberty
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Interoception: the sense of the physiological condition of the body
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Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54
de Roux, N., Genin, E., Carel, J.-C., Matsuda, F., Chaussain, J.-L., & Milgrom, E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1834399100 · Cited by 2,431 · cited 1×
“…women also express kisspeptin (Hrabovszky et al., 2010, 2011; Rometo et al., 2007), another essential peptide for puberty and reproduction (de Roux et al., 2003; Seminara et al., 2003; Topaloglu et al., 2012) and similar to NKB, kisspeptin mRNA is increased in postmenopausal women (Fig.”
BackgroundThe Neuroendocrine Control of the Menstrual Cycle
Knobil, E. (1980) · Elsevier eBooks · doi:10.1016/b978-0-12-571136-4.50008-5 · Cited by 1,285
Regulation of Kiss1 gene expression in the brain of the female mouse
Smith, J. T., Cunningham, M. J., Rissman, E. F., Clifton, D. K., & Steiner, R. A. (2005) · Endocrinology · doi:10.1210/en.2005-0488 · Cited by 1,102
Han, S.-K., Gottsch, M. L., Lee, K. J., Popa, S. M., Smith, J. T., Jakawich, S. K., Clifton, D. K., Steiner, R. A., & Herbison, A. E. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.3328-05.2005 · Cited by 1,036
Topaloglu, A. K., Reimann, F., Guclu, M., Yalin, A. S., Kotan, L. D., Porter, K. M., Serin, A., Mungan, N. O., Cook, J. R., Ozbek, M. N., et al. (2009) · Nature Genetics · doi:10.1038/ng.306 · Cited by 961
Clarke, I. J., & Cummins, J. T. (1982) · Endocrinology · doi:10.1210/endo-111-5-1737 · Cited by 921
Research works printed but not linked: 1
- Wiley, 2005
Cited by
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Treatment of symptoms of the menopause: an Endocrine Society Clinical Practice Guideline
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Sex hormone effects on autonomic mechanisms of thermoregulation in humans
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The thermoregulation system and how it works
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Self-citationTreating menopause — MHT and beyond
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Menopausal Vasomotor Symptoms and Risk of Incident Cardiovascular Disease Events in SWAN
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Sex-Specific Physiology and Cardiovascular Disease
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Onset of the Menopause Transition
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Estrogens and the control of energy homeostasis: a brain perspective
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Managing Menopausal Symptoms and Associated Clinical Issues in Breast Cancer Survivors
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Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause
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Episodic Ultradian Events—Ultradian Rhythms
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Fezolinetant in the treatment of vasomotor symptoms associated with menopause
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Hormones and Aging: An Endocrine Society Scientific Statement
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Vasomotor symptoms: natural history, physiology, and links with cardiovascular health
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Effects of Phoenixin-14 on anxiolytic-like behavior in mice
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Neuropeptide co-expression in hypothalamic kisspeptin neurons of laboratory animals and the human
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The menopausal hot flush: a review
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Sex differences in variability across timescales in BALB/c mice
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Elinzanetant for Vasomotor Symptoms from Endocrine Therapy for Breast Cancer
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Dissecting the Molecular Mechanisms Surrounding Post-COVID-19 Syndrome and Neurological Features
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Metadata
- Authors
- Rance, N. E., Dacks, P. A., Mittelman-Smith, M. A., Romanovsky, A. A., & Krajewski-Hall, S. J.
- Affiliations
- University of Arizona (US)
- Alzheimer's Drug Discovery Foundation (US)
- St. Joseph's Hospital and Medical Center (US)
- Corresponding author
- Rance, Naomi E.
- Venue
- Frontiers in Neuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 34
- Issue
- 3
- Pages
- 211-227
- ISSN
- 0091-3022 (ISSN-L)
- PMC
- PMC3833827
- OpenAlex
- W2061642929
- Semantic Scholar
- 7043397029ae60ac9040a754434a6e725779bcdf
- Cited by
- 380
- References
- 205
- Citations by year
- 2026: 45 · 2025: 52 · 2024: 46 · 2023: 41 · 2022: 28 · 2021: 35 · 2020: 22 · 2019: 24 · 2018: 28 · 2017: 27 · 2016: 10 · 2015: 15 · 2014: 7
- FWCI
- 1.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Frontiers in Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01 NS41233)
- National Institute on Aging (R01 AG032315)
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- hot flashes, KNDy neurons, kisspeptin, neurokinin B, dynorphin, hypothalamus, thermoregulation, estrogen, postmenopausal women, neurokinin-3 receptor, median preoptic nucleus, cutaneous vasodilation, luteinizing hormone secretion, arcuate nucleus
- MeSH terms
- Animals, Body Temperature Regulation, Dynorphins, Estradiol, Female, Humans, Hypothalamus, Luteinizing Hormone, Models, Biological, Neurons, Ovariectomy, Preoptic Area, Skin, Tail, Vasodilation, Neurokinin B, Signal Transduction, Postmenopause, Receptors, Neurokinin-3, Hot Flashes, Estrous Cycle, Rats, Kisspeptins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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