Olster D H, Auerbach I D
Department of Psychology, University of California, Santa Barbara, CA 93106-9660, USA.
Neuroendocrinology. 2000 Dec;72(6):350-9. doi: 10.1159/000054604.
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 microg/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 microg/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 ER alpha ICC. No genotypic differences in the number of cells containing ER alpha-immunoreactivity (-IR) in the medial preoptic area (MPOA), ventromedial hypothalamus (VMH) or arcuate nucleus (ARC) were noted, but obese females had significantly fewer ER alpha-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 microg/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 microg/kg) of EB. These data are consistent with the 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.
肥胖的雌性 Zucker 大鼠（fa/fa）不育。它们的生殖异常包括对卵巢甾体激素对性行为的刺激作用反应低下。本研究旨在验证以下假设：肥胖的 Zucker 雌性大鼠下丘脑/视前区雌激素受体（ERs）和/或雌二醇诱导的孕激素受体（PRs）存在缺陷。对去卵巢（OVX）的瘦型和肥胖型 Zucker 大鼠注射苯甲酸雌二醇（EB，15 或 100 μg/kg）加孕酮（P，2 mg/kg）后，测试其性行为表现。正如预期的那样，在注射较低的生理剂量 EB 后再注射 P，肥胖雌性大鼠的脊柱前凸商和脊柱前凸评分显著低于瘦型动物。相反，在注射 P 之前接受较高剂量 EB 的肥胖和瘦型雌性大鼠表现出相似水平的性接受能力。两周后，这些 OVX 瘦型和肥胖雌性大鼠在灌注和进行 PR 免疫细胞化学（ICC）的组织处理之前，分别注射了溶剂、15 或 100 μg/kg EB。对两种基因型的另外几组 OVX 处女雌性大鼠进行灌注，并对视前区和下丘脑的组织进行 ERα ICC 处理。在内侧视前区（MPOA）、腹内侧下丘脑（VMH）或弓状核（ARC）中，未发现含有 ERα免疫反应性（-IR）的细胞数量存在基因型差异，但肥胖雌性大鼠腹侧室周前核（AVPV）中 ERα-IR 细胞的数量明显少于瘦型大鼠。在两种基因型中，与注射溶剂相比，注射 EB（任一剂量）后 AVPV、MPOA 和 VMH 中 PR-IR 细胞的数量显著增加，表明雌二醇诱导了 PRs。仅在 MPOA 中，肥胖和瘦型雌性大鼠在雌二醇诱导的 PR-IR 方面存在显著差异。接受 15 μg/kg EB 的肥胖雌性大鼠 MPOA 中 PR-IR 细胞的数量少于接受相同处理的瘦型动物。注射溶剂或较高剂量（100 μg/kg）EB 后未观察到这种基因型差异。这些数据与以下假设一致：AVPV 中 ERα和/或 MPOA 中 PRs 的缺陷可能导致肥胖 Zucker 雌性大鼠对卵巢甾体激素反应不佳。
