NEUROENDOCRINE MEDIATION OF SOCIALLY INDUCED ANOVULATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 今年的研究仍在继续，评估由社会从属关系引起的心理社会压力对成年雌性恒河猴代谢、生殖和行为结果的影响。此外，编码5-羟色胺再摄取转运体(5HTTLPR)基因的多态性的贡献也得到了评估，因为其他研究表明，携带短启动子长度变异(S变异)的一个或两个等位基因的个体比携带长启动子长度纯合子的雌性个体(L/L)更容易受到心理社会压力的不利影响。本年度进行了两项实验。最初的研究评估了补充瘦素的效果，以检验瘦素发挥中枢作用的假设，最大限度地减少对心理社会应激源的反应，并确定瘦素是否能使已知的甲状腺激素水平正常化，这些甲状腺激素水平因社会从属关系而受到抑制。第二个实验测试了这样一种假设，即孕酮的神经活性代谢物别孕酮可以缓解焦虑，并在新的情况下减少下丘脑-垂体-肾上腺轴的激活。对这两个实验的数据的分析仍在进行中。在未来的一年里，我们将评估促肾上腺皮质激素释放激素(CRH)拮抗剂对一些代谢和生殖终点的影响，以检验以下假设：在从属女性中观察到的生殖缺陷是CRH上调的结果，并将为患有应激性不孕症的女性提供可能的治疗策略。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Studies have continued this year assessing the consequences of psychosocial stress, resulting from social subordination, on metabolic, reproductive, and behavioral outcomes I adult female rhesus monkeys. In addition, the contribution of polymorphisms in the gene that encodes the serotonin reuptake transporter (5HTTLPR) was evaluated as other studies show individuals carrying one or both alleles of the short promoter length variant (s-variant) are more vulnerable to the adverse consequences of psychosocial stress than females homozygous for the long promoter length (l/l). Two experiments were conducted in the current year. The initial study assessed the effects of supplementation of leptin to test the hypothesis that leptin acts centrally to minimize the response to psychosocial stressors and to determine whether leptin normalizes thyroid hormone levels known to be depressed by social subordination. The second experiment tested the hypothesis that allopregnanolone, a neuroactive metabolite of progesterone, would be anxiolytic and reduce activation of the hypothalamic pituitary adrenal axis to novel situations. The analyses of the data from both of these experiments are still under way. In the coming year, we will assess the effects of a corticotropin releasing hormone (CRH) antagonist on a number of metabolic and reproductive endpoints to test the hypothesis that the reproductive deficits observed in subordinate females are the result of an up-regulation of CRH, and will provide insights into possible treatment strategies for women suffering from stress-induced infertility.