GONADAL-STEROID HORMONES AND HYPOTHALAMIC OPIOID CIRCUITRY

Endogenous Opioid peptides derived from several gene families are loca lized within hypothalamic regions known to be involved in the regulati on of reproduction. For example, the proenkephalin gene products, met- and leu-enkephaiin, and the proopiomelanocortin (POMC) gene product, beta-endorphin, are found in the rat medial preoptic area (MPOA). More over, the expression of these peptides and their receptors varies acro ss the estrous cycle in the female rat. We have examined the gonadal s teroid regulation of mu-opiate receptors and opioid peptides in the MP OA, and POMC mRNA expression in neurons that innervate the MPOA. mu-Op iate receptors in the MPOA are sexually dimorphic and gonadal steroid hormone-dependent. Hormonal priming of ovariectomized rats with estrog en and progesterone (P) upregulates MPOA mu-receptors 27, but not 3, h r after P treatment. Inhibition of protein synthesis during the first 6 hr after P prevents receptor upregulation. The density of beta-endor phin fibers in the MPOA also increases following hormone treatment, an d POMC mRNA expression in neurons that innervate the MPOA is induced b y hormone treatment beginning 13 hr after P treatment. This delayed re sponse might be ubiquitous among POMC neurons, as those innervating th e median eminence also exhibit increased POMC mRNA expression along a similar time course. The results suggest that hormonal feedback regula tes opioid peptides which act at mu-receptors in the MPOA to influence reproductive behavior and cyclicity. These opioid functions represent an important component in the complex regulatory processes which cont rol reproduction. (C) 1994 Academic Press, Inc.