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 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.
Subject(s)
Hydrocortisone/metabolism , Leptin/pharmacology , Macaca mulatta , Social Behavior , Aggression/drug effects , Animal Husbandry , Animals , Behavior, Animal/drug effects , Female , Hierarchy, Social , Humans , Infusion Pumps, Implantable , Infusions, Subcutaneous , Leptin/administration & dosage , Macaca mulatta/physiology , Recombinant Proteins/administration & dosage , Recombinant Proteins/pharmacology , Stress, Psychological/metabolism , Stress, Psychological/physiopathologyABSTRACT
OBJECTIVE: Insulin resistance is greater and obesity is more common in women with preeclampsia. The Trp64Arg polymorphism in the beta(3)-adrenergic receptor is associated with these metabolic changes. This study investigated whether the Trp64Arg polymorphism is more common in women with preeclampsia. STUDY DESIGN: beta(3)-Adrenergic receptor genotypes were determined in 177 women with a history of preeclampsia and in 179 normal pregnancies. We also compared prepregnancy body mass index (BMI), length of gestation, baby weight percentile, and glucose values during an oral tolerance test in women with and without the polymorphism. RESULTS: The genotypes and allele frequency did not differ significantly between women with preeclamptic and normal pregnancies (P=.17). Women with and without the polymorphism had similar prepregnancy BMI, glucose at 1-hour screening, gestational age at delivery, and adjusted baby weight. CONCLUSION: The Trp64Arg polymorphism of the beta(3)-receptor does not predispose to preeclampsia, and it is it not associated with obesity and carbohydrate intolerance in a population of young pregnant women.
