GONADAL-STEROID HORMONE RECEPTORS AND SEX-DIFFERENCES IN THE HYPOTHALAMO-PITUITARY-ADRENAL AXIS

The rapid activation of stress-responsive neuroendocrine systems is a basic reaction of animals to perturbations in their environment. One w ell-established response is that of the hypothalamo-pituitary-adrenal (HPA) axis. In rats, corticosterone is the major adrenal steroid secre ted and is released in direct response to adrenocorticotropin (ACTH) s ecreted from the anterior pituitary gland. ACTH in turn is regulated b y the hypothalamic factor, corticotropin-releasing hormone. A sex diff erence exists in the response of the HPA axis to stress, with females reacting more robustly than males. It has been demonstrated that in bo th sexes, products of the HPA axis inhibit reproductive function. Conv ersely, the sex differences in HPA function are in part due to differe nces in the circulating gonadal steroid hormone milieu. It appears tha t testosterone can act to inhibit HPA function, whereas estrogen can e nhance HPA function. One mechanism by which androgens and estrogens mo dulate stress responses is through the binding to their cognate recept ors in the central nervous system. The distribution and regulation of androgen and estrogen receptors within the CNS suggest possible sites and mechanisms by which gonadal steroid hormones can influence stress responses. In the case of androgens, data suggest that the control of the hypothalamic paraventricular nucleus is mediated trans-synapticall y. For estrogen, modulation of the HPA axis may be due to changes in g lucocorticoid receptor-mediated negative feedback mechanisms. The resu lts of a variety of studies suggest that gonadal steroid hormones, par ticularly testosterone, modulate HPA activity in an attempt to prevent the deleterious effects of HPA activation on reproductive function. ( C) 1994 Academic Press, Inc.