The ovarian steroid hormones estradiol and progesterone are known to exert genomic effects on the hypothalamic ventromedial nucleus (VMN), which in turn promotes the display of sexually receptive behavior. Oxytocin receptor (OTR) binding activity and transcripts are induced by estradiol in the VMN. Central administration of exogenous OT facilitates female sexual behavior, but only in animals pretreated with both estradiol and progesterone. Central antagonism of OTRs, however, blunts this behavior in animals given both estradiol and progesterone, without impairing the sexual behavior shown by animals primed with estradiol alone. Thus, while estradiol is important for inducing OTRs, the effect of estradiol on sexual behavior appears to be independent of OT. On the other hand, the effects of progesterone on sexual behavior seem to involve OT. To further elucidate the biological basis for these steroid-hormone effects on behavior, it would be useful to examine the cellular functions of hypothalamic OTRs. For example, the issue of whether or not increases in OTR binding activity are associated with concomitant increases in second-messenger production remains to be examined. This is especially interesting, given that estradiol-induced OTRs appear to have little behavioral significance in the absence of progesterone. In this regard, it would also be important to examine the post-receptor mechanisms associated with brain OTRs, and whether or not they too are regulated by gonadal steroid hormones. Under this Research Planning Grant, methods will be established to investigate OT-induced second-messenger production in rat-brain membranes. These preliminary studies will set the stage for future experiments designed to investigate the post-receptor consequences of steroid regulation of OTRs in the hypothalamus.
