Deficits in Progesterone-Facilitated Sexual Behaviors and Forebrain Estrogen and Progestin Receptors in Obese Female Zucker Rats

Abstract

Obese female Zucker rats (fa/fa) are sterile. Among their reproductive abnormalities is hyporesponsiveness to the stimulatory effects of ovarian steroid hormones on sexual behaviors. This study was designed to test the hypothesis 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 display of sexual behaviors following injection of estradiol benzoate (EB, 15 or 100 µg/kg) plus progesterone (P, 2 mg/kg). As expected, obese females showed significantly lower lordosis quotients and lordosis ratings than lean animals after injection of the lower, physiological dose of EB followed by P. In contrast, obese and lean females receiving the higher EB dose, prior to P, showed similar levels of sexual receptivity. Two weeks later, these OVX lean and obese females received injections of vehicle, 15 or 100 µg/kg EB, 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 ERα ICC. No genotypic differences in the number of cells containing ERα-immunoreactivity (-IR) in the medial preoptic area (MPOA), ventromedial hypothalamus (VMH) or arcuate nucleus (ARC) were noted, but obese females had significantly fewer ERα-IR cells in the anteroventral periventricular nucleus (AVPV) than lean rats. In both genotypes, the number of PR-IR cells in the AVPV, MPOA and VMH was significantly higher following injection of EB (either dose) as compared to vehicle, demonstrating estradiol induction 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 µg/kg EB had fewer PR-IR cells in the MPOA than comparably-treated lean animals. No such genotypic difference was observed following injection of the vehicle or higher dose (100 µg/kg) of EB. These data are consistent with the hypothesis that deficiencies in ERα in the AVPV and/or PRs in the MPOA may contribute to obese Zucker females’ poor responsiveness to ovarian steroid hormones.