Administration of human leptin differentially affects parameters of cortisol secretion in socially housed female rhesus monkeys

Chronic exposure to psychosocial stress may lead to a dysregulation of the limbic-hypothalamic-pituitary-adrenal axis that results in a number of adverse health outcomes. The fat-derived hormone leptin has been indicated as a potential key component to maintaining homeostasis by enhancing glucocorticoid negative feedback. Using an established model of nonhuman primate social stress, notably social subordination, this study examined the effects of continuous leptin administration on cortisol secretion in female rhesus monkeys. The 20 subjects were maintained in stable five-member social groups with established dominance hierarchies. All females were ovariectomized but received estradiol throughout the study to maintain serum concentrations at early follicular phase levels. Three parameters of cortisol secretion were examined in dominant and subordinate females during control and leptin-treatment conditions: diurnal cortisol secretion; response to a dexamethasone suppression test; and response to a brief separation from their social group. We hypothesized that leptin supplementation would attenuate the hypercortisolemia characteristic of subordinate females. During baseline conditions, subordinate female rhesus monkeys had significantly lower levels of serum leptin compared with more dominant monkeys and were less sensitive to glucocorticoid negative feedback. Exogenous administration of leptin improved glucocorticoid negative feedback in subordinate females and decreased morning cortisol in all animals. However, there were no status differences in response to a social separation test and diurnal rhythm in cortisol during baseline conditions. However, leptin administration did not attenuate the increase in cortisol in response to a social separation. The data presented in this study demonstrate that leptin can attenuate several parameters of cortisol secretion in female rhesus monkeys and thus may play a role in the response of the adrenal glands to socio-environmental stimuli.