Deficits in progesterone-facilitated sexual behaviors and forebrain estrogen and progestin receptors in obese female Zucker rats

Obese female Zucker rats (fa/fa) are sterile. Among their reproductive abno rmalities is hyporesponsiveness to the stimulatory effects of ovarian stero id hormones on sexual behaviors. This study was designed to test the hypoth esis that obese Zucker females are deficient in hypothalamic/preoptic area estrogen receptors (ERs) and/or estradiol-induced progestin receptors (PRs) . Ovariectomized (OVX) lean and obese Zucker rats were tested for the displ ay of sexual behaviors following injection of estradiol benzoate (EB, 15 or 100 mug/kg) plus progesterone (P, 2 mg/kg). As expected, obese females sho wed significantly lower lordosis quotients and lordosis ratings than lean a nimals after injection of the lower, physiological dose of EB followed by P . In contrast, obese and lean females receiving the higher EB dose, prior t o P, showed similar levels of sexual receptivity. Two weeks later, these OV X lean and obese females received injections of vehicle, 15 or 100 mug/kg E B, prior to perfusion and tissue processing for PR immunocytochemistry (ICC ). Additional groups of OVX virgin females of both genotypes were perfused and tissue from the preoptic area and hypothalamus was processed for ER alp ha ICC. No genotypic differences in the number of cells containing ER alpha -immunoreactivity (-IR) in the medial preoptic area (MPOA), ventromedial h ypothalamus (VMH) or arcuate nucleus (ARC) were noted, but obese females ha d significantly fewer ER alpha -IR cells in the anteroventral periventricul ar nucleus (AVPV) than lean rats. In both genotypes, the number of PR-IR ce lls in the AVPV, MPOA and VMH was significantly higher following injection of EB (either dose) as compared to vehicle, demonstrating estradiol inducti on of PRs. Only in the MPOA was there a significant difference between fat and lean females in estradiol-induced PR-IR. Obese females receiving 15 mug / kg EB had fewer PR-IR cells in the MPOA than comparably-treated lean anim als. No such genotypic difference was observed following injection of the v ehicle or higher dose (100 mug/kg) of EB. These data are consistent with th e hypothesis that deficiencies in ER alpha: in the AVPV and/ or PRs in the MPOA may contribute to obese Zucker females' poor responsiveness to ovarian steroid hormones. Copyright (C) 2000 S. Karger AG, Basel.