NEUROENDOCRINE BASES OF REPRODUCTIVE BEHAVIOR

如果一个人接受行为是神经元的产物这一观点 活跃性，那么就有理由研究激素的影响。 在调节激素调节的神经回路中的脑细胞 行为。我们认为去甲肾上腺素的激素依赖性变化 (NE)下丘脑和视前区的神经传递 参与雌性雌激素和孕酮的调节 生殖行为。这个实验室的初步工作 表明给予生理相关剂量的 E(2)和P在体内调节两种NE受体的信号转导 下丘脑和丘脑的β和α1肾上腺素受体亚型 视前区。这项拟议研究的目标是阐明 雌激素和孕激素调节信号转导的分子机制(S) 下丘脑和视前区的β和α1肾上腺素能受体 并将这些与前凸行为的表达联系起来。第一 一系列实验验证了E2调节α1-的假设 肾上腺素受体基因的表达，更具体地说，肾上腺素受体基因的表达 Alpha1B亚型。这是一个重要的问题，因为NE刺激 α1-肾上腺素能受体促进发情行为和促性腺激素 雌激素性雌性大鼠体内释放。使用分子技术(Northern 斑点杂交、定量原位杂交)和受体 放射自显影：E2和α1的时间和剂量依赖效应 受体的mRNA和蛋白将在特定的下丘脑中被量化 和视前区核团，并与易化相关。 前凸行为。我们还将确定Alpha1的诱导 受体存在于表达E2受体的神经元中。功能界别 将通过评估偶联来监测α1受体的活性 α1a和α1B受体亚型与cAMP和 作为类固醇功能的磷酸肌醇第二信使系统 治疗。这些研究应该会提供对分子的洞察 磷对前凸的快速、协同作用机制 注射雌激素的动物的反应性。第二系列实验 测试了E2也通过基因组机制起作用的假设 脱敏下丘脑和视前区的β-肾上腺素能受体功能 区域。这是一个重要的问题，因为 E_2促进生殖行为可能是通过减弱 β受体介导的抑制作用。时间和剂量- E_2对β受体刺激cAMP生成的依赖作用 将与促进前凸行为相关。在……里面 此外，雌激素减敏β受体介导的机制 信令将被识别。

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.