Effect of ovarian hormones and estrous cycle on stimulation of the hypothalamo-pituitary-adrenal axis by cocaine

Cocaine is known to exert sexually dimorphic HPA axis effects in rats and t o disrupt estrous cyclicity and/or fertility in rats, nonhuman primates, an d humans. The present studies investigated the reciprocal interactions betw een ovarian hormones and HPA axis responses to cocaine. Thirty minutes afte r injection, cocaine (15 mg/kg i.p.) increased serum ACTH and corticosteron e more in cycling than ovariectomized females or male rats. ACTH and cortic osterone were highest in proestrus when estradiol was elevated. Cocaine did not alter serum estradiol in females or testosterone in males but did stim ulate progesterone secretion in both sexes. Cocaine-stimulated progesterone secretion was significantly greater in females than in males or ovariectom ized females, and greater in proestrous than diestrous 1 rats. Cocaine stim ulated corticosterone and progesterone secretion in sham-adrenalectomized, but not adrenalectomized rats, indicating that the adrenal gland and not th e ovary is the source of cocaine-stimulated progesterone. Estrogen influenc ed cocaine-stimulated progesterone secretion more than corticosterone, sugg esting different release mechanisms for the two steroids in the adrenal. Th ese results suggest that adrenally derived progesterone could contribute to cocaine-induced physiological changes, including inhibited gonadotropin re lease.