Cited by 179Stress Responses and CortisolEstrogen and related hormone effectsAdrenal Hormones and Disorders

Glucocorticoid hormone resistance during primate evolution: receptor-mediated mechanisms

Open access
Chrousos, G P, Renquist, D, Brandon, D, Eil, C, Pugeat, M, Vigersky, R, Cutler, G B, Loriaux, D L +1 more·1982·Proceedings of the National Academy of Sciences

Abstract

The concentrations of total and protein-unbound plasma cortisol of New World monkeys are higher than those of Old World primates and prosimians. The urinary free-cortisol excretion also is increased markedly. However, there is no physiologic evidence of increased cortisol effect. These findings suggest end-organ resistance to glucocorticoids. This was confirmed by showing that the hypothalamic-pituitary adrenal axis is resistant to suppression by dexamethasone. To study this phenomenon, glucocorticoid receptors were examined in circulating mononuclear leukocytes and cultured skin fibroblasts from both New and Old World species. The receptor content is the same in all species, but the New World monkeys have a markedly decreased binding affinity for dexamethasone. Thus, the resistance of these species to the action of cortisol is due to the decreased binding affinity of the glucocorticoid receptor. This presumed mutation must have occurred after the bifurcation of Old and New World primates (approximately 60 x 10(6) yr ago) and before the diversion of the New World primates from each other (approximately 15 x 10(6) yr ago).

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Crossref · 10.1073/pnas.79.6.2036

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Authors
Chrousos, G. P., Renquist, D., Brandon, D., Eil, C., Pugeat, M., Vigersky, R., Cutler, G. B., Loriaux, D. L., & Lipsett, M. B.
Affiliations
National Institutes of Health (US)
Venue
Proceedings of the National Academy of Sciences
Published
1982-03
Volume
79
Issue
6
Pages
2036-2040
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2073621450
Cited by
179
References
32
Citations by year
2026: 1 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 7 · 2019: 2 · 2018: 5 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 2 · 2013: 4 · 2012: 3
FWCI
1.90
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords
glucocorticoid resistance, glucocorticoid receptor, New World monkeys, Old World primates, prosimians, cortisol, urinary free cortisol, hypothalamic-pituitary-adrenal axis, mononuclear leukocytes, dermal fibroblasts, primate evolution, receptor mutations
MeSH terms
Animals, Dexamethasone, Biological Evolution, Humans, Hydrocortisone, Leukocytes, Primates, Protein Binding, Receptors, Glucocorticoid, Receptors, Steroid, Species Specificity

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