Neuroendocrine Bases of Reproductive Behavior

生殖行为的神经内分泌基础

• 批准号: 6621142
• 负责人: ANNE M ETGEN
• 金额: $ 30.06万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6621142
• 关键词: alpha adrenergic receptor; behavioral /social science research tag; biological signal transduction; calcium channel; calcium flux; cyclic GMP; enzyme activity; estradiol; female reproductive system; hormone regulation /control mechanism; hypothalamus; immunocytochemistry; insulinlike growth factor; laboratory rat; luteinizing hormone; mitogen activated protein kinase; neuroendocrine system; neurons; nitric oxide; norepinephrine; phosphatidylinositol 3 kinase; preoptic areas; progesterone; receptor expression; sex behavior; western blottings

DESCRIPTION (provided by applicant): The ovarian hormones estradiol (E2) and progesterone (P) act in the hypothalamus (HYP) and preoptic area (POA) to ensure that the preovulatory luteinizing hormone (LH) surge coincides with reproductive behavior (lordosis), thereby maximizing reproductive success. We propose that E2 and P-dependent changes in norepinephrine (NE) synaptic activity in the HYP and POA are key mediators of the neuroendocrine integration of reproduction. We propose further that insulin-like growth factor-I (IGF-1) and its receptor (IGF-1R) mediate certain reproductive actions of E2 in the HYP-POA and engage in cross talk with NE receptors in these brain areas. The proposed research will elucidate the molecular mechanism(s) by which E2 and P interact with IGF-1 R and a1-adrenergic receptor signaling pathways in the HYP and POA and will relate these to lordosis behavior. Specific Aim 1 tests the hypothesis that IGF-1 Rs mediate E2 actions in the HYP-POA that are involved in female reproductive function via activation of phosphoinositide 3-kinase (PI3-K) or mitogen-activated protein kinase (MAPK). We will assess (a) E2 facilitation of lordosis behavior; (b) E2-induced increases in IGF-1 R density in the HYPPOA; (c) E2+P-induced coupling of a1-adrenoceptors to cGMP synthesis in the HYP-POA; and (d) E2-induced increases in spine density on ventromedial hypothalamic neurons. Specific Aim 2 tests the hypothesis that E2+P-dependent linkage of a1-adrenoceptors to cGMP also results in activation of MAPK signaling in the HYP and POA. Specific Aim 3 tests the hypothesis that in the HYP-POA of E2-treated rats, P switches a1-adrenoceptor signaling to synthesis of cGMP, which mediates NE facilitation of lordosis, by elevating intracellular calcium. We will determine whether a1-adrenoceptors stimulate cGMP formation by activating: (a) extracellular calcium influx via N and/or L-type calcium channels; (b) intracellular calcium mobilization from the endoplasmic reticulum; (c) release of ryanodine-sensitive calcium stores; and/or (d) growth factor-regulated kinases such as src or P13-K. Specific Aim 4 will determine how IGF-1 acutely potentiates a1-adrenoceptor signaling in the HYP-POA of E2-treated females and whether this is important for reproductive behavior.

描述（由申请人提供）：卵巢激素雌二醇（E2）和 孕酮（P）在下丘脑（HYP）和poA前（POA）中作用 确保排卵前黄体激素（LH）激增与 生殖行为（Lordosis），从而最大程度地发挥了生殖成功。我们 提出去甲肾上腺素（NE）突触的E2和P依赖性变化 催眠和POA的活动是神经内分泌整合的关键介体 繁殖。我们进一步提出，胰岛素样生长因子I（IGF-1） 及其受体（IGF-1R）介导了E2的某些生殖作用 在这些大脑区域中与NE受体进行交叉交谈。这 拟议的研究将阐明E2和P的分子机制 与IGF-1 R和催眠中的A1-肾上腺素能受体信号通路相互作用 和POA，并将这些与Lordosis行为联系起来。特定的目标1测试 IGF-1 RS介导HYP-POA中E2作用的假设 女性生殖功能通过激活磷酸肌醇3-激酶 （PI3-K）或有丝分裂原激活的蛋白激酶（MAPK）。我们将评估（a）E2 促进行为的促进； （b）E2诱导的IGF-1 R密度增加 在hyppoa中； （C）E2+P诱导的A1肾上腺素受体与CGMP合成的耦合 在催眠中； （d）E2诱导的腹侧脊柱密度增加 下丘脑神经元。特定目标2检验了E2+p依赖性的假设 A1-肾上腺素受体与CGMP的链接也导致MAPK激活 在催眠和POA中发出信号。特定目的3检验了以下假设 E2处理的大鼠的HYP-POA，P开关为合成的A1-肾上腺素受体信号传导 CGMP通过抬高细胞内介导了Lordosis的NE促进。 钙。我们将确定A1-肾上腺素受体是否通过 激活：（a）通过N和/或L型钙的细胞外钙涌入 频道； （b）内质的细胞内钙动员 网状（c）释放ryanodine敏感的钙储存；和/或（d）增长 因子调节的激酶，例如SRC或P13-K。具体目标4将决定 IGF-1如何急性增强A1-肾上腺素受体信号传导 E2处理的女性以及这对于生殖行为重要。