Administration of human leptin differentially affe

Authors: Lynn A Collura Jackie B Hoffman Mark E Wilson

Publish Date: 2009/10/24

Volume: 36, Issue: 3, Pages: 530-537

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Abstract

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 fatderived 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 fivemember 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 leptintreatment 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 socioenvironmental stimuliThe technical assistance of Jeffrey Fisher Jennifer Whitley and Holly Jarrell is greatly appreciated This study was funded by NIH grants HD46501 training Grants nos 4425 RR024505 for LAC and K12 GM000680 for JBH and in part RR00165 The YNPRC is fully accredited by AAALAC International

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