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Cited by 61Stress Responses and CortisolNeuropeptides and Animal PhysiologyAdrenal Hormones and Disorders

Studies of the Regulation of the Hypothalamic-Pituitary-Adrenal Axis in Sheep with Hypothalamic-Pituitary Disconnection. II. Evidence for in Vivo Ultradian Hypersecretion of Proopiomelanocortin Peptides by the Isolated Anterior and Intermediate Pituitary*

ENGLER, DENNIS, PHAM, THAO, LIU, JUN-PING, FULLERTON, MERYL J., CLARKE, IAIN J., FUNDER, JOHN W.·1990·Endocrinology
DOI 10.1210/endo-127-4-1956
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Abstract

Studies were performed to determine whether the isolated ovine anterior and intermediate pituitary might rhythmically secrete three POMC peptides, ACTH, ir-β-endorphin (ir-β-EP), and ir-α-melanocyte stimulating hormone (ir-α- MSH) in vivo. When blood was taken at 10-min intervals from four ewes with hypothalamo-pituitary-disconnection (HPD), a distinct POMC-peptide and cortisol ultradian rhythm was noted. A comparison of the four HPD ewes with five nonstressed hypothalamopituitary-intact (HPI) ewes revealed that the mean plasma levels of the three POMC-peptides and cortisol were increased, the mean ACTH and ir-α-MSH pulse amplitudes were increased, and the mean ir-β-EP and ir-α-MSH interpulse intervals were decreased. When four HPI ewes were subjected to a mild stress, plasma POMC-peptide and cortisol levels increased significantly when compared with the five unstressed HPI animals. In addition, the ACTH and cortisol pulse amplitudes increased and the ir-β-EP and ir-α-MSH interpulse intervals decreased. Although plasma ACTH levels in the stressed HPI and HPD ewes were comparable, mean plasma cortisol levels were 2-fold greater in the stressed HPI animals. To determine whether the ACTH hypersecretion in the HPD ewe might reflect a net reduction in hypothalamic inhibitory influence over ACTH secretion, we examined the effects of dopamine (DA), somatostatin (SS-14), and rat atrial natriuretic peptide [rANF(l-28)] on the secretion of ACTH from cultured ovine anterior pituitary cells. DA and SS-14 did not exert a discernible effect on basal, CRF-, or arginine vasopressin (AVP)- stimulated ACTH secretion. Although basal ACTH secretion was unaffected by rANF(l-28) (10-12-10-8 M), a significant inhibition of CRF- and AVP-stimulated ACTH release was observed. Furthermore, when 100 μg rANF(l-28) was injected via the external carotid artery into four HPD ewes, the rise in plasma ACTH and cortisol did not differ from that seen in four HPD ewes injected with NaCl. We conclude that: 1) pulsatile POMC-peptide secretion is an intrinsic property of the corticotrope and melanotrope; 2) POMC-peptide secretion in the HPI ewe represents the modification of this intrinsic pituitary rhythm by the hypothalamus; 3) in the HPI ewe, activation of the hypothalamus by mild stress increases plasma ACTH to levels seen in the HPD ewe, and increases both the ACTH pulse frequency and pulse amplitude; 4) the increased plasma levels of ir-β-EP and ir-α-MSH and decreased ir-β-EP interpulse interval after HPD suggests that the neural input to the intermediate lobe restrains intermediate lobe POMC-peptide secretion; 5) the increased plasma ACTH and cortisol levels after HPD suggests that the hypothalamus also exerts a tonic inhibitory influence over POMC peptide synthesis and/or secretion by the anterior pituitary; however, this putative inhibitory influence is not mediated by dopamine or SS-14; 6) the ability of ANF(l-28) to inhibit CRF- or AVPmediated ACTH secretion in vitro suggests that the ovine corticotrope may possess intracellular mechanisms that inhibit ACTH secretion which are distinct from those which mediate the feedback actions of the glucocorticoids. (Endocrinology127: 1956–1966,1990)

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  • In sheep with surgical disconnection of the hypothalamus from the pituitary, pulsatile cortisol secretion is maintained despite loss of a normal response to stress.

    “These animals still maintain pulsatile cortisol secretion, despite their loss of a normal response to stress (Engler et al. 1990).”

    From Origin of ultradian pulsatility in the hypothalamic–pituitary–adrenal axis (2010) · cites this paper as Engler et al. 1990

  • Blocking the effect of CRH on the pituitary did not eliminate the pulsatile release of ACTH.

    “However, blocking the effect of CRH on the pituitary did not eliminate the pulsatile release of ACTH (51).”

    From Modeling the hypothalamus-pituitary-adrenal axis: A review and extension (2015) · cites this paper as [51]

  • In the experiment presented in (51), the pituitary was only isolated from the CRH impact and it could interact with the rest of the body.

    “However, in the experiment presented in (51), the pituitary was only isolated from the CRH impact and it could interact with the rest of the body.”

    From Modeling the hypothalamus-pituitary-adrenal axis: A review and extension (2015) · cites this paper as [51]

  • The present paper's model does not have an ultradian pulse generator solely located in hypothalamus, a paradigm going back to Engler et al. [14].

    “whereas the model in the present paper does not have an ultradian pulse generator solely located in hypothalamus, a paradigm going back to Engler et al. [14].”

    From Patient specific modeling of the HPA axis related to clinical diagnosis of depression (2017) · cites this paper as [14]

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Authors
ENGLER, D., PHAM, T., LIU, J.-P., FULLERTON, M. J., CLARKE, I. J., & FUNDER, J. W.
ORCID
Venue
Endocrinology
Publisher
The Endocrine Society
Published
1990-10
Volume
127
Issue
4
Pages
1956-1966
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/endo-127-4-1956
OpenAlex
W2005476222
Cited by
61
References
44
Citations by year
2025: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 4 · 2017: 1 · 2016: 5 · 2015: 5 · 2014: 6 · 2013: 3 · 2012: 1
FWCI
0.90
Type
journal article
Language
en
Open access
closed
Locations
  • Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institutes of Health
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords
hypothalamic-pituitary-adrenal axis, ultradian rhythms, ACTH secretion, cortisol, anterior pituitary, atrial natriuretic peptide, dopamine, somatostatin, corticotropin-releasing factor, vasopressin, stress response, sheep, pulsatile hormone secretion
MeSH terms
Adrenal Glands, Adrenocorticotropic Hormone, alpha-MSH, Animals, beta-Endorphin, Dopamine, Female, Hydrocortisone, Hypothalamus, Atrial Natriuretic Factor, Periodicity, Pituitary Gland, Pituitary Gland, Anterior, Pro-Opiomelanocortin, Sheep, Somatostatin

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