NEUROENDOCRINE REGULATION OF REPRODUCTIVE FUNCTION

该项目研究动物生殖的神经内分泌控制。 和人类受试者，重点是a)排卵周期的调节 和间歇性促性腺激素分泌；b)季节性的光周期控制 生殖；c)下丘脑和哺乳期闭经；d)早产 卵巢衰竭；和e)黄体期焦虑症： (A)排卵周期：黄体酮在调节 对骑自行车的妇女和大鼠的排卵进行了研究。在女性身上，封锁 排卵前黄体酮的升高持续推迟排卵， 黄体酮的作用相反，表明一个重要的 黄体酮在排卵时间中的作用。在大鼠中，信使核糖核酸 下丘脑CRH和前阿片黑素皮质素(POMC)有明显的变化 大约在排卵期促性腺激素激增的时候，这表明在 阿片肽也可能调节这种激增。POMC的变化与那些 黄体酮水平。 (B)光周期：以前的研究已经确定光周期很强 调节恒河猴的生殖功能。松果体切除术被废除 这些反应使动物要么是非循环的要么是自由奔跑的 循环。 (C)哺乳期闭经：哺乳期闭经妇女接受 搏动性促性腺激素释放激素。这一方案恢复了周期 卵巢功能达到与对照组相同的程度， 说明哺乳期月经周期的中断是 完全处于中心位置。因为阿片类药物可以导致下丘脑闭经，CRH 和POMC基因在哺乳期发情大鼠中的表达。两种多肽 信息显著减少。 (D)卵巢早衰：在患者和小鼠身上进行了研究 自身免疫性卵巢疾病模型。与正常更年期相比，许多人 POF患者被发现有卵泡，这使得 减刑的可能性。在A/J小鼠品系中，新生儿胸腺切除 导致自身免疫性卵巢衰竭的克隆性缺失失败； 然而，其他菌株在胸腺切除后没有表现出疾病，这表明 可选择的容忍机制。 (E)LLPDD：症状与周期黄体期之间的联系 用黄体酮拮抗剂截断黄体期进行研究。 尽管荷尔蒙发生了变化，但症状的时间进程与 对照组。这一发现表明，我们应该重新评估 LLPDD是一种固有的周期性疾病，周期作为一种 Zeitgeber。

This project studies the neuroendocrine control of reproduction in animals and human subjects, with focus on a) the regulation of the ovulatory cycle and episodic gonadotropin secretion; b) photoperiodic control of seasonal reproduction; c) hypothalamic and lactational amenorrhea; d) premature ovarian failure; and e) luteal phase dysphoric disorder: (A) Ovulatory Cycle: The role of progesterone in the regulation of ovulation was studied in cycling women and in rats. In women, blockade of the preovulatory rise in progesterone consistently delayed ovulation, an effect reversed with progesterone administration, indicating an important role for progesterone in the timing of ovulation. In rats, mRNA's for hypothalamic CRH and pro-opiomelanocortin (POMC) showed marked variations around the time of the ovulatory gonadotropin surge, suggesting that in opiate peptides may also modulate the surge. POMC changes paralleled those of levels of progesterone. (B) Photoperiodism: Previous work has established that photoperiod strongly modulates reproductive function in rhesus monkeys. Pinealectomy abolishes these responses and leaves animals either acyclic or with free-running cycles. (C) Lactational Amenorrhea: Lactating amenorrheic women were treated with pulsatile gonadotropin-releasing hormone. This regimen restored cyclic ovarian function to a degree identical to that of control subjects, indicating that the interruption of the menstrual cycle during lactation is entirely central. Because opioids can underlie hypothalamic amenorrhea, CRH and POMC mRNA's were studied in lactating anestrus rats. Both peptide messages were markedly reduced. (D) Premature Ovarian Failure (POF): was studied in patients and in a mouse model of autoimmune ovarian disease. In contrast to normal menopause, many patients with POF were found to have follicles, which allows the possibility of remission. In the A/J mouse strain, neonatal thymectomy leads to failure of clonal deletion with autoimmune ovarian failure; however, other strains do not manifest disease after thymectomy, indicating alternative mechanisms of tolerance. (E) LLPDD: The linkage between symptoms and the luteal phase of the cycle was studied by truncating the luteal phase with a progesterone antagonist. Despite the hormonal changes, symptoms followed the same time course as in the control groups. This finding suggests a re-evaluation of the biology of LLPDD as an intrinsically periodic disorder for which the cycle serves as a Zeitgeber.