NEURAL ANDROGEN RECEPTORS FACILITATING COPULATION

这项研究的目的是了解性腺的活动。 类固醇对大脑中控制男性的雄激素和雌激素受体的影响 性行为。叙利亚仓鼠是一个合适的动物模型 这些研究是因为男性依赖于这两种化学感觉刺激 和性腺激素来诱导交配，以及通过 调节这一行为的大脑是已知的。嗅觉和犁鼻 化学感觉刺激通过一系列神经元进行处理，这些神经元 选择性地从血液中摄取雄激素和雌激素，两者 这些信号(气味和荷尔蒙)对于正常交配是必不可少的 发生。 我们的初步研究描述了类固醇受体的位置- 含神经元和受体从核到核的重新分配 用免疫细胞化学方法检测激素停用后的细胞质。在第一个 具体目的，我们将通过以下方式确定基本的神经生物学机制 哪些性腺激素通过自身调节来刺激交配 它们的受体。首先，我们将确定雄激素如何影响 用原位杂交和免疫组织化学方法检测其在脑内的受体水平 受体结合法定量测定脑内雄激素受体的mRNA和蛋白 性腺完整且被阉割的雄性。其次，时间进程和剂量- 神经雄激素受体对睾酮激活的反应将是 用免疫细胞化学方法测定。最后，我们将本地化未绑定 神经元内超微结构水平的细胞质雄激素受体 被阉割的雄性。在具体目标2中，我们将重点介绍功能 含雄激素和雌激素受体神经元的种群 控制性行为。特别是，我们的研究将集中在 杏仁内侧核(Me)，终纹床核 (BNST)和内侧视前区(MPOA)是潜在的 化学感觉和荷尔蒙信号的整合，以进行交配。我们会 确定新生儿激素暴露在性二型性疾病中的作用 雄激素受体在MPOA中的分布模式。此外，联合本地化 雄激素和雌激素受体的免疫反应性将决定 单个神经元对两种性腺类固醇都有反应。最后，我们会 用脑内植入雌激素和DHT来确定Me和MPOA 诱导类固醇信号的同一性(雄激素或雌激素) 在这些脑区交配。 所提出的研究对了解神经功能具有重要意义。 在合成类固醇的影响下。滥用这些物质是 成为我们社会的一个严重的健康问题。这些关于 雄激素受体在脑内的定位和激素调节 将为研究行为效应提供必要的基础。 外源性雄激素。

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.