Cited by 557Stress Responses and CortisolAdrenal Hormones and DisordersNeuropeptides and Animal Physiology

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Regulation of Pituitary ACTH Secretion during Chronic Stress

Aguilera, Greti·1994·Frontiers in Neuroendocrinology

DOI 10.1006/frne.1994.1013

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Abstract

Maintenance of adequate levels of response of the hypothalamic-pituitary-adrenal axis during chronic stress is important for survival. Three basic patterns of response can be identified depending on the type of stress: (a) desensitization of ACTH responses to the sustained stimulus, but hyperresponsiveness to a novel stress despite elevated plasma glucocorticoid levels, as occurs in physical-psychological paradigms; (b) no desensitization of ACTH response to the repeated stimulus and hyperresponsiveness to a novel stress, as occurs during repeated painful stress and insulin hypoglycemia; and (c) small and transient increases in ACTH, but sustained elevations of plasma corticosterone and diminished ACTH responses. The level of response of the pituitary corticotroph is determined by differential regulation of the hypothalamic regulators, corticotropin-releasing hormone (CRH) and vasopressin (VP), and the sensitivity of the negative glucocorticoid feedback. While osmotic stimulation increases VP expression in magnocellular neurons of the paraventricular (PVN) and supraoptic nuclei of the hypothalamus, chronic stress paradigms with high pituitary responsiveness are associated with activation of CRH and CRH/VP parvicellular neurons of the PVN, predominantly of the VP-containing population. While moderate increase of CRH output is important for stimulation of POMC transcription, the increase of the VP:CRH secretion ratio appears to be important in maintaining the secretory capacity of the pituitary corticotroph during chronic stimulation. Decreased sensitivity of the glucocorticoid feedback, probably due to interaction of glucocorticoid receptors with transcription factors induced by CRH and VP, is critical for the maintenance of ACTH responses in the presence of elevated plasma glucocorticoid levels during chronic stress. Although both CRH and VP receptors are activated and undergo regulatory variations during chronic stress, only the changes in VP receptor levels are parallel to the changes in pituitary ACTH responsiveness. The inhibitory effect of chronic osmotic stimulation on ACTH secretion in spite of high circulating levels of VP is probably the result of diminished activity of parvicellular PVN neurons and downregulation of pituitary VP receptors. Although the exact interaction between regulatory factors and the molecular mechanisms controlling the sensitivity of the corticotroph during adaptation to chronic stress remain to be determined, it is clear that regulation of the proportional secretion of CRH and VP in the PVN, modulation of pituitary VP receptors, and the sensitivity to feedback inhibition play a critical role.

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Background
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Background
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Background
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Background
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“Because there is a shift in colocalization from predominant CRH production to AVP synthesis in PVN, therefore some authors suggested AVP as the main hypothalamic regulator of the HPA axis during chronic stress [53, 54].”
Kinetics and Persistence of Cardiovascular and Locomotor Effects of Immobilization Stress and Influence of ACTH Treatment
Sabban, E. L., Schilt, N., Serova, L. I., Masineni, S. N., & Stier, C. T. (2008) · Neuroendocrinology · doi:10.1159/000150099 · Cited by 11
“Several patterns of ACTH responses have been identified depending on the stress paradigm and influenced by differential regulation of hypothalamic regulators corticotrophin releasing hormone (CRH) and vasopressin [9].”
Background
Behavioral sensitization to intermittent morphine in mice is accompanied by reduced adrenocorticotropine but not corticosterone responses
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Vasopressin-induced presynaptic facilitation of sympathetic neurotransmission in the pithed rat
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“, 1996) including a prolonged stimulation of the hypothalamic–pituitary–adrenocortical (HPA) axis, a key biological component of the stress response (Aguilera, 1994).”
Background
Urofaecal glucocorticoid metabolite concentrations in African penguin (Spheniscus demersus) chick populations experiencing different levels of human disturbance
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“Additionally, although an organism may perceive the presence of humans as a threat, chronic exposure can result in the desensitization of adrenocorticotropic hormone responsiveness, and thus the reduction of the resultant stress response mechanism and baseline GC levels (Aguilera, 1994).”
Background
Acute ether stress differentially affects corticotropin-releasing factor and urocortin 1 in the Brattleboro rat
Sterrenburg, L., Borch, A., Peeters, B. W. M. M., Pintér, O., Zelena, D., Roubos, E. W., & Kozicz, T. (2011) · Brain Research · doi:10.1016/j.brainres.2011.04.047 · Cited by 10
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“In vivo studies have shown that the ACTH responses to both AVP and CRH undergo regulatory changes during chronic stress (Aguilera 1994).”
BackgroundInfluential
Role of Endogenous Nociceptin in the Regulation of Arginine Vasopressin Release in Conscious Rats
Kakiya, S. (2000) · Endocrinology · doi:10.1210/en.141.12.4466 · Cited by 10
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“One of the main endocrine mechanisms is the activation of the hypothalamic–pituitary–adrenal (HPA) axis (Aguilera 1994).”
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Effects of early tooth loss on the hippocampus in senescence-accelerated mice
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Does mental arithmetic before head up tilt have an effect on the orthostatic cardiovascular and hormonal responses?
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Koko, V., Djordjevic, J. D., Cvijić, G., & Davidović, V. (2006) · Journal of Thermal Biology · doi:10.1016/j.jtherbio.2006.01.009 · Cited by 9
Neuroendocrinology and Behavior
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Quantitative Analysis of Corticotropin‐Releasing Factor and Arginine Vasopressin mRNA in the Hypothalamus During Chronic Morphine Treatment in Rats: AnIn SituHybridization Study
Laorden, M. L., Milanés, M. V., Angel, E., et al. (2003) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.2003.01037.x · Cited by 9
Stress Adaptation and the Hypothalamic‐Pituitary‐Adrenal Axis
Aguilera, G. (2016) · Wiley eBooks · doi:10.1002/9781118760369.ch17 · Cited by 8
Self-citation
Adrenocorticotropic Hormone
Rhodes, M. E. (2017) · Stress: Neuroendocrinology and Neurobiology · doi:10.1016/b978-0-12-802175-0.00010-3 · Cited by 9
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Stojiljković, A. S., Čupić, Ž., Maćešić, S., Ivanović-Šašić, A., & Kolar-Anić, L. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.976323 · Cited by 9
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In vitro effect of cortisol and urotensin I on arginine vasotocin and isotocin secretion from pituitary cells of gilthead sea bream Sparus aurata
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“Other findings indicate that the expression of AVP in parvocellular neurons of the PVN and AVP secretion into the pituitary portal circulation increases under chronic stress in rats (Holmes et al., 1986; de Goeij et al., 1992; Aguilera, 1994; Chowdrey et al., 1995).”
Result
Gender‐specific Regulation of the Hypothalamo‐pituitary‐adrenal axis and the Role of Vasopressin during the Neonatal Period
Makara, G. B., Domokos, Á., Mergl, Z., Csabai, K., Barna, I., & Zelena, D. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1410.002 · Cited by 8
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“Further, enhanced glucocorticoid concentrations subsequently suppress the pituitary expression of POMC, resulting in reduced levels of ACTH and α-MSH (Aguilera, 1994; Drouin et al., 1989; Slominski et al., 2000).”
Background
Vasopressin Receptors: Structural Functional Relationships and Role in Neural and Endocrine Regulation
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Androgen receptors in corticotropin-releasing hormone neurons mediate the sexual dimorphism in restraint-induced thymic atrophy
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The Influence of Different Light Spectra on Broiler Chicken Endocrine Systems and Productivity
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The effects of chronic restraint stress on empathy-like behaviour in rats
Şen, A., Kara, A. Y., Koyu, A., Şimşek, F., Kızıldağ, S., & Uysal, N. (2021) · Neuroscience Letters · doi:10.1016/j.neulet.2021.136255 · Cited by 8

Authors: Aguilera, G.
Affiliations: National Institutes of Health (US)
Corresponding author: Aguilera, Greti
Venue: Frontiers in Neuroendocrinology
Publisher: Elsevier BV
Published: 1994-12
Volume: 15
Issue: 4
Pages: 321-350
ISSN: 0091-3022 (ISSN-L)
DOI: 10.1006/frne.1994.1013
OpenAlex: W2031934304
Cited by: 557
References: 0
Citations by year: 2026: 10 · 2025: 11 · 2024: 14 · 2023: 16 · 2022: 11 · 2021: 12 · 2020: 11 · 2019: 14 · 2018: 11 · 2017: 17 · 2016: 21 · 2015: 19 · 2014: 14 · 2013: 18 · 2012: 18
FWCI: 5.50
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Frontiers in Neuroendocrinology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords: ACTH secretion, chronic stress, hypothalamic-pituitary-adrenal axis, corticotropin-releasing factor, vasopressin, corticotrophs, glucocorticoid negative feedback, paraventricular nucleus, supraoptic nucleus, osmotic stimulation, glucocorticoid receptor, stress adaptation, corticosterone, insulin-induced hypoglycemia
MeSH terms: Adrenocorticotropic Hormone, Animals, Corticosterone, Corticotropin-Releasing Hormone, Glucocorticoids, Homeostasis, Humans, Hypothalamus, Pituitary Gland, Stress, Physiological, Vasopressins

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Regulation of Pituitary ACTH Secretion during Chronic Stress

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