NEURAL ANDROGEN RECEPTORS FACILITATING COPULATION

神经雄激素受体促进交配

基本信息

批准号：
2403481
负责人：
RUTH I. WOOD
金额：
$ 10.75万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-07-01 至 1999-06-30
项目状态：
已结题

项目摘要

The objectives of this research are to understand the actions of gonadal steroids on androgen and estrogen receptors in the brain that control male sexual behavior. The Syrian hamster is an appropriate animal model for these studies beacuse the male is dependent upon both chemosensory stimuli and gonadal hormones to elicit mating, and the basic pathways through the brain that mediate this behavior are known. Olfactory and vomeronasal chemosensory stimuli are processed through a chain of neurons that selectively take up androgens and estrogens from the bloodstream, and both of these signals (odors and hormones) are essential for normal mating to occur. Our preliminary studies have described the locations of steroid receptor- containing neurons and the repartitioning of the receptor from nucleus to cytoplasm after hormone withdrawal using immunocytochemistry. In the first Specific Aim, we will determine essential neurobiological mechanisms by which gonadal hormones stimulate copulation through autoregulation of their receptor. First, we will determine how androgens influence the levels of their receptor in the brain using in situ hybridization and receptor binding to quantify androgen receptor mRNA and protein in brains of gonad-intact and castrate males. Secondly, the time-course and dose- response to testosterone activation of neural andogen receptors will be determined using immunocytochemistry. Finally, we will localize unbound cytoplasmic androgen receptor at the ultrastructural level within neurons of castrated males. In Specific Aim 2, we will focus on functional populations of androgen and estrogen receptor-containing neurons controlling sexual behavior. In particular, our studies will focus on the medial amygdaloid nucleus (Me), bed nucleus of the stria terminalis (BNST), and the medial preoptic area (MPOA) as potential sites for the integration of chemosensory and hormonal signals for copulation. We will determine the role of neonatal steroid exposure in the sexually dimorphic pattern of androgen receptors in MPOA. In addition, colocalization of androgen and estrogen receptor immunoreactivity will determine if individual neurons can respond to both gonadal steroids. Finally, we will use intracerebral implants of estrogen and DHT in Me and MPOA to determine the identity (androgen or estrogen) of steroid signals that induce copulation in these brain areas. The proposed studies have significance to understanding neural function under the influence of anabolic steroids. Abuse of these substances is becoming a serious health problem in our society. These observations on the location and hormonal regulation of androgen receptors in the brain will provide an essential basis for studying the behavioral effects of exogenous androgens.

这项研究的目标是了解性腺的行为控制雄性的雄激素和雌激素受体上的类固醇性行为。叙利亚仓鼠是适合的动物模型这些研究对男性的依赖于两个化学感应刺激和性腺激素以引起交配，以及穿过的基本途径介导这种行为的大脑是已知的。嗅觉和呕吐化学感应刺激是通过一系列神经元处理的有选择地从血液中占据雄激素和雌激素，两者都这些信号（气味和激素）对于正常交配至关重要发生。我们的初步研究描述了类固醇受体的位置含有神经元和受体从核转化为戒断激素后使用免疫细胞化学的细胞质。在第一个具体目的，我们将通过性腺激素通过自动调节而刺激了交配他们的受体。首先，我们将确定雄激素如何影响使用原位杂交和受体结合以量化大脑中的雄激素受体mRNA和蛋白性腺直觉和cast割男性。其次，时间和剂量 - 对睾丸激素的反应神经和基因受体的激活将是使用免疫细胞化学确定。最后，我们将本地化无限神经元内超微结构水平的细胞质雄激素受体 cast割的男性。在特定目标2中，我们将专注于功能雄激素和含雌激素受体神经元的种群控制性行为。特别是，我们的研究将集中于内侧杏仁核（ME），质子末端的床核（BNST）和内侧前区域（MPOA）作为潜在部位化学体和激素信号的整合以进行交配。我们将确定新生儿类固醇暴露在性二态中的作用 MPOA中雄激素受体的模式。另外，共定位雄激素和雌激素受体免疫反应性将确定是否是否单个神经元可以对两种性腺类固醇反应。最后，我们会的在ME和MPOA中使用雌激素和DHT的脑内植入物来确定诱导类固醇信号的身份（雄激素或雌激素）这些大脑区域的交配。提出的研究对于理解神经功能具有重要意义在合成代谢类固醇的影响下。这些物质的滥用是成为我们社会的严重健康问题。这些观察大脑中雄激素受体的位置和激素调节将为研究的行为影响提供重要的基础外源雄激素。