HORMONES, NEURONAL PHOSPHOPROTEINS AND BEHAVIOR

描述(摘自申请者的摘要)：卵巢类固醇 激素，雌二醇和黄体酮，调节细胞功能 中枢神经系统导致生理和神经功能改变 行为。就像在其他生殖组织中一样，雌激素的神经效应 黄体酮对性行为的影响被认为需要他们的 激素敏感中与同源细胞内受体的相互作用 神经元。类固醇受体在配体调控转录中的作用 激素结合后发生构象变化的因子，允许 激素受体复合体与激素反应的紧密联系 靶基因上的元件并影响参与神经网络的 对性行为的控制。已知许多神经递质是 参与类固醇激素影响的神经元过程 雌性哺乳动物的性行为。神经递质多巴胺的作用 关于雌性啮齿类动物的性行为已被证明发生在 膜上多巴胺受体与细胞内的串扰 黄体酮受体。而细胞和分子机制 参与这一法规背后的相互作用并不是很好 理解，假设这可能通过磷酸化的方式发生 黄体酮受体。在拟议的研究中，信号转导 调节串扰的途径将通过识别 类固醇激素诱导/磷酸化神经元磷酸蛋白和 多巴胺。这些磷蛋白与类固醇的相互作用 将检查雌激素和黄体酮等激素。会是 确定磷蛋白是否使黄体酮磷酸化 受体本身或调节辅调节蛋白，从而激活 受体和促进性行为。这些磷蛋白将会是 在下丘脑周围类固醇受体丰富的区域描绘 以及邻近的大鼠大脑的视前区，已知的区域是 与多巴胺和黄体酮促进的性行为有关。 最后，孕酮的转录激活功能结构域 参与多巴胺激活的受体或其 辅助性蛋白质将被测定。

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.