Glucocorticoid hormone resistance during primate evolution: receptor-mediated mechanisms

G. P. Chrousos, D. Renquist, D. Brandon, C. Eil, M. Pugeat, R. Vigersky, G. B. Cutler, D. L. Loriaux, M. B. Lipsett

Research output: Contribution to journalArticle

155 Scopus citations

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 (≃60 x 106 yr ago) and before the diversion of the New World primates from each other (≃15 x 106 yr ago).

Original languageEnglish (US)
Pages (from-to)2036-2040
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume79
Issue number6 I
DOIs
StatePublished - Dec 29 1982

ASJC Scopus subject areas

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