HORMONES, NEURONAL PHOSPHOPROTEINS AND BEHAVIOR

描述（改编自申请人的摘要）：卵巢类固醇 激素，雌二醇和孕酮，调节细胞功能， 中枢神经系统，导致生理变化， 行为 与其他生殖组织一样，雌二醇的神经效应 和黄体酮对性行为的影响， 与激素敏感性细胞中的同源细胞内受体的相互作用 神经元 类固醇受体作为配体调节的转录 在激素结合后发生构象变化的因子， 激素受体复合物与激素反应的紧密联系 靶基因上的元素，并影响参与 控制性行为。 已知许多神经递质 参与类固醇激素影响的神经过程 雌性哺乳动物的性行为 神经递质多巴胺的作用 对雌性啮齿动物性行为的影响已经被证明是通过 多巴胺的膜受体和细胞内 孕酮受体 虽然细胞和分子机制 参与这种调节的相互作用的人并不好， 可以理解，假设这可能通过磷酸化 孕酮受体 在拟议的研究中，信号转导 将通过识别 类固醇激素诱导/磷酸化的神经元磷蛋白， 多巴胺 这些磷蛋白与类固醇激素的相互作用 将检查激素雌二醇和孕酮。 将 确定磷蛋白是否磷酸化孕酮 受体本身或调节辅调节蛋白，从而激活 受体和促进性行为。 这些磷蛋白将 下丘脑周围富含类固醇受体的区域 和邻近的大鼠大脑视前区， 参与多巴胺和孕酮促进的性行为。 最后，孕酮的转录激活功能域 受体参与多巴胺激活受体或其 将测定辅助蛋白。

DESCRIPTION (adapted from applicant's abstract): The ovarian steroid hormones, estradiol and progesterone, regulate cellular functions in the central nervous system resulting in the alterations in physiology and behavior. As in other reproductive tissues, the neural effects of estradiol and progesterone on sexual behavior are believed to require their interaction with cognate, intracellular receptors in the hormone sensitive neurons. Steroid receptors function as ligand-regulated transcription factors which undergo conformational change upon hormone binding, permitting tight association of the hormone-receptor complexes with hormone response elements on the target genes and affect neural networks involved in the control of sexual behavior. Numerous neurotransmitters are known to be involved in the neuronal processes by which steroid hormones influence sexual behavior in female mammals. The effects of neurotransmitter dopamine on sexual behavior in female rodents has been demonstrated to occur by means of cross-talk between membrane receptors for dopamine and intracellular progesterone receptors. While the cellular and molecular mechanisms involved in the interactions underlying this regulation are not well understood, it is assumed that this may occur via the phosphorylation of progesterone receptors. In the proposed research, the signal transduction pathways mediating the cross talk will be elucidated by identifying the neuronal phosphoproteins induced/phosphorylated by steroid hormones and dopamine. The interactions between these phosphoproteins and steroid hormones, estradiol and progesterone, will be examined. It will be determined whether the phosphoproteins phosphorylate the progesterone receptor per se or modulate the coregulator proteins, thereby activating the receptor and facilitating sexual behavior. These phosphoproteins will be delineated in the steroid receptor-rich regions surrounding the hypothalamus and the adjacent pre-optic area of the rat brain the areas known to be involved in the dopamine and progesterone-facilitated sexual behavior. Finally, the transcription activation functional domains of progesterone receptor involved in the dopamine activation of the receptor or its accessory proteins will be determined.