NEURAL ANDROGEN RECEPTORS FACILITATING COPULATION

本研究的目的是了解性腺的活动， 类固醇对大脑中雄激素和雌激素受体的影响， 性行为叙利亚仓鼠是一种合适的动物模型， 这些研究是因为雄性依赖于两种化学感觉刺激， 和性腺激素来引发交配，以及通过 调节这种行为大脑是已知的。嗅觉和犁鼻 化学感觉刺激通过一系列神经元处理， 选择性地从血液中摄取雄激素和雌激素， 这些信号（气味和激素）是正常交配所必需的， 发生. 我们的初步研究已经描述了类固醇受体的位置- 含有神经元和受体从核到神经元的再分配 用免疫细胞化学方法检测激素撤除后的细胞质。上 具体目标，我们将确定基本的神经生物学机制， 哪些性腺激素通过自动调节 他们的受体。首先，我们将确定雄激素如何影响 使用原位杂交检测其在大脑中的受体水平， 受体结合以定量脑中雄激素受体mRNA和蛋白 生殖腺完整和阉割的雄性其次，时间进程和剂量- 对睾酮激活神经雄激素受体的反应将是 用免疫细胞化学测定。最后，我们将本地化未绑定 细胞质雄激素受体在神经元内超微结构水平 被阉割的雄性在具体目标2中，我们将重点关注功能 含雄激素和雌激素受体的神经元群 控制性行为特别是，我们的研究将集中在 杏仁内侧核，终纹床核 （BNST），和内侧视前区（MPOA）作为潜在的网站， 结合化学感受和激素信号进行交配。我们将 确定新生儿类固醇暴露在性二型性发育中的作用 MPOA中雄激素受体的模式。此外， 雄激素和雌激素受体免疫反应性将决定 单个神经元可以对两种性腺类固醇都有反应。最后我们将 在Me和MPOA中使用脑内植入雌激素和二氢睾酮来确定 类固醇信号的身份（雄激素或雌激素）诱导 在这些大脑区域交配。 这些研究对理解神经功能具有重要意义 在合成代谢类固醇的影响下滥用这些物质是 成为我们社会中一个严重的健康问题。这些意见， 大脑中雄激素受体的位置和激素调节 将为研究行为影响提供必要的基础， 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.