STERIOD HORMONES-BRAIN & BGEHAVIOR

类固醇激素-大脑

• 批准号: 3486777
• 负责人: ANNE M ETGEN
• 金额: $ 13.85万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-01 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3486777
• 关键词: adrenergic receptor; alpha adrenergic receptor; enzyme mechanism; epinephrine; estradiol; estrogen receptors; estrus; experimental brain lesion; gender difference; hormone regulation /control mechanism; hypothalamus; laboratory rat; neuroendocrine system; neurotransmitter metabolism; neurotransmitters; progesterone; sex behavior; stereotaxic techniques; synaptosomes; tyrosine 3 monooxygenase

The long-term objective of this research is to establish how hormonal signals are recognized by brain cells and subsequently translated into specific changes in behavior. To accomplish this goal, studies are focused on elucidating the mechanisms by which the ovarian steroid hormones regulate the expression of one component of female reproductive behavior, the lordosis response. Previous work has provided evidence that estrogenic facilitation of lordosis involves receptor-mediated regulation of gene expression in neurons of the ventromedial hypothalamus (VMH). The research described in this proposal uses a combination of behavioral and biochemical techniques to test the hypothesis that ovarian steroid induction of lordosis in female rats is mediated by augmentation of norepinephrine (NE) transmission in or near the VMH. Specific experiments will ask: (1) Does steroid activation of lordosis behavior require NE transmission in or near the VMH? If so, which NE receptor subtype(s) mediate the effects of NE on lordosis? (2) Do hormone treatments which facilitate lordosis behavior augment basal and/or evoked release of NE in or near the VMH? (3) Are the facilitatory and inhibitory effects of other neurotransmitters and neuromodulators on steroid-dependent lordosis mediated by alterations in NE release in or near the VMH? (4) Are sex differences in steroid facilitation of lordosis responsiveness due to sex differences in hormonal regulation of NE transmission in or near the VMH? (5) Do ovarian steroids regulate activity of tyrosine hydroxylase, the rate-limiting enzyme in NE synthesis, in or near the VMH? If so, are soluble and/or synaptosomal tyrosine hydroxylase the target of regulation, and what is the mechanism of regulation? The new information provided by these studies will form the foundation for future work, the ultimate goal of which is to define the precise molecular mechanisms by which hormones act in brain tissue to bring about specific behavioral changes. Clarification of the effects of ovarian steroids on NE transmission in the brain may allow us to develop testable hypotheses regarding the relationships among hormones, premenstrual complaints, postmenopausal complaints, stress, depression and anxiety. In addition, studies on sex differences in neurotransmitter regulation might yield insight into sex differences in the occurrence of psychiatric illnesses and the neural responses to therapeutic agents, such as antidepressants.

这项研究的长期目标是确定如何 激素信号由脑细胞识别，随后识别 翻译成特定的行为变化。 实现这一目标 目标，研究的重点是阐明其机制 卵巢类固醇激素调节一个 女性生殖行为的组成部分，Lordosis反应。 以前的工作提供了雌激素促进的证据 脊柱肌的涉及受体介导的基因调节 腹侧下丘脑（VMH）的神经元中的表达。 该提案中描述的研究结合了 行为和生化技术来检验以下假设 卵巢类固醇诱导雌性大鼠的dorlosisos诱导是由 在或附近的去甲肾上腺素（NE）的增强 VMH。 具体实验会询问： （1）脊lordosis行为的类固醇激活需要NE 在VMH中还是附近的传输？ 如果是这样，哪个NE受体 亚型介导了NE对Lordosis的影响？ （2）做激素治疗，促进脊柱障碍行为 增强基底和/或诱发NE在VMH中或附近的NE释放？ （3）是其他的促进和抑制作用 依赖类固醇的神经递质和神经调节剂 Lordosis介导的，是由NE释放的改变或附近的NE释放的改变 VMH？ （4）是类固醇促进的性别差异 由于性别差异的荷尔蒙调节，响应能力 NE在VMH中还是附近的传输？ （5）卵巢类固醇调节酪氨酸羟化酶的活性， NE合成中的限速酶，在VMH中还是附近？ 如果 因此，是可溶性和/或突触体酪氨酸羟化酶 调节的目标，调节的机理是什么？ 这些研究提供的新信息将构成 未来工作的基础，其最终目标是定义 激素在大脑中作用的精确分子机制 组织会带来特定的行为变化。 澄清 卵巢类固醇对大脑NE传播的影响 可能使我们能够提出有关有关的可检验的假设 激素之间的关系，经前投诉， 绝经后投诉，压力，抑郁和焦虑。 在 补充，关于神经递质调节性别差异的研究 可能会对发生性别差异的见解 精神病和对治疗的神经反应 药物，例如抗抑郁药。