Effect of dehydroepiandrosterone on central and peripheral levels of allopregnanolone and beta-endorphin

OBJECTIVE: To evaluate the effects of dehydroepiandrosterone (DHEA) oral administration on neuroendocrine function by investigating the modulation exerted by DHEA administration on allopregnanolone and beta-endorphin (beta-EP) central and peripheral levels in ovariectomized rats. DESIGN: Prospective study. SETTING(S): Experimental research environment. ANIMAL(S): Female Wistar rats (n = 48). INTERVENTION(S): Forty rats were ovariectomized and received an oral treatment with either placebo or 0.5, 1, or 2 mg/kg/day of DHEA. After euthanization, beta-EP levels were measured in hippocampus, hypothalamus, anterior pituitary, neurointermediate pituitary, and plasma. Allopregnanolone and DHEAS levels were measured in hippocampus, hypothalamus, anterior pituitary, adrenal glands, and serum. Serum E(2) concentration was also measured. MAIN OUTCOME MEASURE(S): Dehydroepiandrosterone sulfate ester (DHEAS), E(2), beta-EP, and allopregnanolone levels. RESULT(S): Dehydroepiandrosterone administration increased DHEAS content in all organs and serum, except for anterior pituitary, where no significant changes occurred. DHEA administration in ovariectomized animals did not significantly increase E(2) circulating levels. DHEA administration induced an increase in allopregnanolone and beta-EP content in hippocampus, hypothalamus, and anterior pituitary and in serum or plasma. CONCLUSION(S): Dehydroepiandrosterone administration in ovariectomized animals increased allopregnanolone and beta-EP central and peripheral levels, which suggests that this compound may play a role as a neuroendocrine mediator, possibly substantiating the beneficial effects of postmenopausal DHEA therapy on the central nervous system.