Glucocorticoid hormone resistance during primate evolution: receptor-mediated mechanisms

Area of Science:

• Endocrinology
• Primate Physiology
• Molecular Biology

Background:

• New World monkeys display elevated plasma cortisol and urinary free-cortisol excretion compared to Old World primates.
• Despite high cortisol levels, physiological evidence suggests reduced cortisol effects in New World monkeys.
• This points towards potential end-organ resistance to glucocorticoids in these species.

Purpose of the Study:

• To investigate the phenomenon of apparent end-organ resistance to glucocorticoids in New World monkeys.
• To compare glucocorticoid receptor characteristics between New World and Old World primates.
• To elucidate the molecular basis for glucocorticoid resistance in New World monkeys.

Main Methods:

• Assessed hypothalamic-pituitary adrenal axis response to dexamethasone suppression.
• Examined glucocorticoid receptor content in mononuclear leukocytes and skin fibroblasts.
• Measured dexamethasone binding affinity to glucocorticoid receptors in different primate species.

Main Results:

• New World monkeys demonstrated resistance of the hypothalamic-pituitary adrenal axis to dexamethasone suppression.
• Glucocorticoid receptor content was similar across New and Old World primate species.
• A markedly decreased binding affinity for dexamethasone was observed in New World monkey glucocorticoid receptors.

Conclusions:

• The observed glucocorticoid resistance in New World monkeys is attributed to a decreased binding affinity of the glucocorticoid receptor.
• This specific receptor characteristic is likely a result of a mutation that occurred after the primate Old/New World divergence.
• The findings provide insight into the evolutionary adaptations of hormone receptor function in primates.