Effects of vasopressin and elimination of corticotropin–releasing hormone–target cells on pro–opiomelanocortin mRNA levels and adrenocorticotropin secretion in ovine anterior pituitary cells
Abstract
Although arginine-vasopressin (AVP) is reported to produce greater ACTH biosynthetic and secretary responses than does corticotropin-releasing hormone (CRH) in sheep anterior pituitary cells, neither factor appears to increase pro-opiomelanocortin (POMC) mRNA levels, as does CRH in the cells of some other species. Since only a fraction of cells that express POMC mRNA may be able to respond to AVP, the aim of this study was to further delineate the regulation of POMC mRNA in ovine anterior pituitary corticotrophs, as a whole and in functional subpopulations of corticotrophs. We measured the effects of AVP, CRH or activation of protein kinase C by phorbol myristate acetate (PMA) in cultured cells. We compared responses in intact populations with those of cultures from which CRH-target cells were pharmacologically eliminated. Dissociated adult ovine anterior pituitary cells were cultured overnight, treated with either vehicle (intact) or a CRH-toxin conjugate that specifically eliminates CRH-target cells (CRH-target-depleted), washed, returned to culture and subsequently challenged with vehicle, AVP (100 nM), CRH (10 nM) or PMA (1 microM) for 5 h. The media were assayed for ACTH by RIA and the cells for POMC mRNA by Northern blot analysis. In intact populations, AVP and CRH increased ACTH secretion from 6.5 +/- 1.2 to 216 +/- 22 and 81 +/- 14 ng/well respectively, but only AVP caused an increase in steady-state POMC mRNA levels (+48 +/- 10%). Direct activation of protein kinase C with PMA mimicked the effect of AVP on ACTH secretion (318 +/- 16 ng/well), but did not alter POMC mRNA levels. In CRH-target-depleted populations, control ACTH secretion (11 +/- 3 ng/well) and POMC mRNA (+69 +/- 7%) were elevated, compared with intact populations. AVP (55 +/- 8 ng/well) and PMA (120 +/- 17 ng/ well), but not CRH, increased ACTH secretion; POMC mRNA was not significantly elevated by any of the treatments. Taken together, these data provide further support for the notion of dissociation between secretion of ACTH and expression of POMC mRNA, and demonstrate that AVP increases steady-state POMC mRNA levels in ovine anterior pituitary cells. The data are also consistent with the concept that complex interactions, possibly including those between cells, influence ACTH secretion and steady-state POMC mRNA levels.
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Both CRH and AVP act on their own receptors on corticotrope cells in the anterior pituitary to stimulate ACTH production and release, with different or even similar potencies.
“Namely, it has been indicated that both CRH and AVP act on their own receptors (28–32) on corticotrope cells in anterior pituitary to stimulate adrenocorticotropic hormone (ACTH) production and release with different (26, 33–41) or even similar potencies (42).”
From Influence of arginine vasopressin on the ultradian dynamics of Hypothalamic-Pituitary-Adrenal axis (2022) · cites this paper as [33]
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Backholer, K., Smith, J. T., Rao, A. V. N., Pereira, A., Iqbal, J., Ogawa, S., Li, Q., & Clarke, I. J. (2010) · Endocrinology · doi:10.1210/en.2009-1190 · Cited by 289 · see citing works
“The cDNA and plasmid inserts used were a 375-base ovine Kiss1 sequence (31), a 400-base ovine POMC sequence (32), and a 511-base rat NPY sequence donated by Dr.”
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Denef, C. (2007) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2007.01616.x · Cited by 244 · see citing works
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Dimerization Between Vasopressin V1b and Corticotropin Releasing Hormone Type 1 Receptors
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“…the most convincing evidence for the necessity of CRHR1 and V1bR interaction is that elimination of CRH-responsive cells using a cytotoxin prevents the stimulatory effect of AVP on proopiomelanocortin (POMC) mRNA, but not the ability of AVP to stimulate ACTH secretion (van de Pavert et al., 1997).”
Backholer, K., Bowden, M. A., Gamber, K. M., Bjørbæk, C., Iqbal, J., & Clarke, I. J. (2009) · Neuroendocrinology · doi:10.1159/000260060 · Cited by 57 · see citing works
Self-citationHenry, B. A., Rao, A., Ikenasio, B. A., Mountjoy, K. G., Tilbrook, A. J., & Clarke, I. J. (2001) · Brain Research · doi:10.1016/s0006-8993(01)02918-3 · Cited by 49 · see citing works
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The influence of sex and gonadectomy on the hypothalamo-pituitary-adrenal axis of the sheep
Canny, B., O'Farrell, K., Clarke, I. J., & Tilbrook, A. J. (1999) · Journal of Endocrinology · doi:10.1677/joe.0.1620215 · Cited by 39 · see citing works
“The RNA was hybridised with a 32P-labelled ovine POMC probe (van der Pavert et al. 1997).”
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Poisbeau, P., Aouad, M., Gazzo, G., Lacaud, A., Kemmel, V., Landel, V., Lelièvre, V., & Feron, F. P. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-1582-6 · Cited by 39 · see citing works
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Functional heterogeneity of corticotrophs in the anterior pituitary of the sheep fetus
Butler, T. G., Schwartz, J., & McMillen, I. C. (1999) · The Journal of Physiology · doi:10.1111/j.1469-7793.1999.0907u.x · Cited by 17 · see citing works
“Furthermore, after elimination of the CRH target cells in the adult pituitary, the remaining AVPresponsive cells secrete the same or more ACTH as in the intact population, although fewer corticotrophs are present (van de Pavert et al. 1997).”
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“The POMC mRNA was detected using a 400-base pair (bp) ovine POMC cDNA probe [22].”
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“(non-CRF responsive) corticotropes (42).”
Wang, S., Matthews, S. G., Yang, K., & Challis, J. R. G. (1998) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-76-9-843 · Cited by 8 · see citing works
Influence of arginine vasopressin on the ultradian dynamics of Hypothalamic-Pituitary-Adrenal axis
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“The phenomenon of the putative local inhibitor of corticotrophs by a substance produced in CRH-target cells was addressed in a series of studies on ovine AP cells (van de Pavert et al., 1997).”
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“The observation that peripheral ACTH levels were unaffected is consistent with previous work in which arginine vasopressin–responsive (AVP-responsive) corticotrophs were found to be responsible for the majority of baseline ACTH secretion, while CRH-responsive corticotrophs were responsible for ACTH release in response…”
ResultTortoriello, D. V. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0216700 · Cited by 4 · see citing works
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Molecular Pathology of Corticotroph Function
Clark, A., & Swords, F. M. (2001) · KARGER eBooks · doi:10.1159/000060866 · Cited by 1 · see citing works
A Hierarchical Model of the Hypothalamo-Adreno-Pituitary systemPreprint
Rota, C. L., Vuza, D. T., & Climescu-Haulica, A. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/837724
Chapter 10: Biology of Stress in Livestock and Poultry
(2017) · CRC Press eBooks · doi:10.1201/9781315152080-15
MYERS, D. (1999) · Endocrinology · doi:10.1210/en.140.9.4292
“(non-CRF responsive) corticotropes (42).”
BackgroundTortoriello, D. V. (2002) · Journal of Clinical Investigation · doi:10.1172/jci200216700
Stress in Domestic Animals: The Roles of the Adrenal Chromaffin and Cortical Tissue
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- Authors
- van de Pavert, S. A., Clarke, I. J., Rao, A., Vrana, K. E., & Schwartz, J.
- Affiliations
- Pennsylvania State University (US)
- Wake Forest University (US)
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 1997-07-01
- Volume
- 154
- Issue
- 1
- Pages
- 139-147
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W1986450670
- Cited by
- 35
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2022: 1 · 2020: 1 · 2019: 2 · 2017: 1
- FWCI
- 2.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1r21aa010555-01)
- Medical Research Council
- National Institute on Alcohol Abuse and Alcoholism (AA10555)
- 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
- vasopressin, corticotropin-releasing factor, ACTH secretion, corticotrophs, protein kinase C, phorbol myristate acetate, sheep
- MeSH terms
- Adrenocorticotropic Hormone, Animals, Arginine Vasopressin, Cells, Cultured, Corticotropin-Releasing Hormone, Dose-Response Relationship, Drug, Female, Pituitary Gland, Anterior, Pregnancy, Pro-Opiomelanocortin, Protein Kinase C, Radioimmunoassay, RNA, Messenger, Sheep, Tetradecanoylphorbol Acetate, Blotting, Northern
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