Glucocorticoid Hormone Resistance during Primate Evolution: Receptor-Mediated Mechanisms

• Published in: Proceedings of the National Academy of Sciences - PNAS 1982-03, Vol.79 (6), p.2036-2040
• Main Authors: Chrousos, G. P., Renquist, D., Brandon, D., Eil, C., Pugeat, M., Vigersky, R., Cutler, G. B., Loriaux, D. L., Lipsett, M. B.
• Format: Article
• Language: English
• Subjects: Animals; Biological Evolution; Blood plasma; cortisol; Dexamethasone - pharmacology; Fibroblasts; Glucocorticoid receptors; Glucocorticoids; Humans; Hydrocortisone - blood; Hydrocortisone - urine; Leukocytes - metabolism; Monkeys; Mononuclear leukocytes; Owls; Primates; Primates - physiology; Protein Binding; Receptors; Receptors, Glucocorticoid - drug effects; Receptors, Steroid - drug effects; resistance; Saimiri sciureus; Species Specificity; Squirrels
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.79.6.2036

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× 106yr ago) and before the diversion of the New World primates from each other (≈ 15× 106yr ago).