NEUROENDOCRINE BASES OF REPRODUCTIVE BEHAVIOR

如果一个人接受这样的观点，即行为是神经系统的产物， 活动，那么检查激素的影响是合理的 在神经回路中的脑细胞上， 行为。 我们认为，去甲肾上腺素依赖性变化 (NE)下丘脑和视前区的神经传递 参与雌激素（E2）和孕激素（P）的调节 生殖行为 本实验室的初步工作 表明施用生理相关剂量的 E（2）和P在体内通过两种NE受体调节信号转导 亚型，β-和α 1-肾上腺素受体，在下丘脑和 视前区 这项研究的目的是阐明 E2和P调节信号转导的分子机制 通过下丘脑和视前区的β和α 1肾上腺素受体 并将这些与脊柱前凸行为的表达联系起来。 第一 一系列的实验验证了E2调节α 1的假设， 肾上腺素受体基因表达，更具体地， α 1B亚型 这是一个重要的问题，因为NE刺激 α 1-肾上腺素能受体促进发情行为和促性腺激素 在E2致敏的雌性大鼠中释放。 使用分子技术（北方 印迹，定量原位杂交）和受体 放射自显影，E2和α 1的时间和剂量依赖性效应 受体mRNA和蛋白质将在特定的下丘脑中定量 和视前区核团，并与促进 脊柱前凸行为。 我们还将确定是否诱导α 1 受体发生在表达E2受体的神经元中。 功能 α 1受体的活性将通过评估偶联 α 1A和α 1B受体亚型对cAMP和 作为类固醇功能的磷酸肌醇第二信使系统 治疗 这些研究应该提供深入了解分子 P对脊柱前凸的快速协同作用机制 在E2-primed动物中的反应。 第二系列的实验 测试E2也通过基因组机制起作用的假设， 使下丘脑和视前区的β-肾上腺素受体功能脱敏 区 这是一个重要的问题，因为 E2对生殖行为的促进作用可能是减弱了 由β受体介导的抑制作用。 时间和剂量 E2对β受体刺激cAMP形成的依赖性作用 将与脊柱前凸行为的促进相关。 在 此外，E2脱敏β受体介导的 将识别信令。

If one accepts the view that behavior is the product of neuronal activity, then it is reasonable to examine the influence of hormones on brain cells in the neural circuits that mediate hormone-regulated behaviors. We propose that hormone-dependent changes in norepinephrine (NE) neurotransmission in the hypothalamus and preoptic area participate in estradiol (E2) and progesterone (P) regulation of female reproductive behavior. Preliminary work from this laboratory demonstrates that administration of physiological relevant doses of E(2) and P in vivo modulates signal transduction by two NE receptor subtypes, beta- and alpha1-adrenoceptors, in the hypothalamus and preoptic area. The goal of the proposed research is to elucidate the molecular mechanism(s) by which E2 and P modulate signal transduction by beta and alpha1-adrenoceptors in the hypothalamus and preoptic area and to relate these to the expression of lordosis behavior. The first series of experiments test the hypothesis that E2 regulates alpha1- adrenoceptor gene expression, and more specifically, expression of the alpha1B subtype. This is a significant question because NE stimulation of alpha1-adrenoceptors facilitates estrous behavior and gonadotropin release in E2-primed female rats. Using molecular techniques (Northern blots, quantitative in situ hybridization) and receptor autoradiography, the time- and dose-dependent effects of E2 and alpha1 receptor mRNA and protein will be quantified in specific hypothalamic and preoptic area nuclei and correlated with the facilitation of lordosis behavior. We will also determine whether induction of alpha1 receptors occurs in neurons that express E2 receptors. The functional activity of alpha1 receptors will be monitored by assessing coupling of alpha1A and alpha1B receptor subtypes to both the cAMP and phosphoinositol second messenger systems as a function of steroid treatment. These studies should provide insight into the molecular mechanisms underlying the rapid, synergistic effects of P on lordosis responsiveness in E2-primed animals. The second series of experiments tests the hypothesis that E2 also acts by genomic mechanisms to desensitize beta-adrenoceptor function in the hypothalamus and preoptic area. This is an important question because a critical component of E2 facilitation of reproductive behavior may be the attenuation of inhibitory actions mediated by beta receptors. The time- and dose- dependent effects of E2 on beta receptor stimulation of cAMP formation will be correlated with the facilitation of lordosis behavior. In addition, the mechanism by which E2 desensitizes beta receptor-mediated signaling will be identified.