CONTROL OF GONADOTROPIN SECRETION DURING LACTATION

哺乳期哺乳期的生殖状态，这种状态发生在所有哺乳动物身上， 与抑制生殖周期有关，而且 促性腺激素释放激素抑制所致排卵 促性腺激素释放激素(GnRH)，调节下丘脑的神经内分泌神经元 繁殖。我们研究的重点是识别传入 哺乳期受哺乳刺激激活的神经元通路 对GnRH神经元功能有抑制作用。 在过去的一年里，我们做了以下观察：1)使用神经元 轨迹追踪技术和共聚焦显微镜，我们已经证明 哺乳刺激对脑区NPY神经元的激活作用 含有GnRH神经元，并与GnRH神经元突起接触。 这些结果表明，哺乳的神经机制可能是 抑制GnRH神经元活动。2)食物摄入量的大幅增加 在哺乳期，最有可能发生的是对 代谢活动的信号变化，如瘦素(a 饱腹感诱导物质)和刺鼠相关转录本(ART， 导致肥胖)。在哺乳期，血液中的瘦素水平极大地 抑制，而ART在下丘脑的表达增加。 目前在实验室中的研究正在研究这种关系 瘦素和ART的变化与神经肽Y神经元增加之间的关系 活动量和食物摄入量。此外，我们正在探索可能的 食物摄入量调节与促性腺激素的相互作用 哺乳期释放激素神经元活性。这很好 确定了不孕不育的许多原因与 能量平衡，如运动性闭经和 神经性厌食症。对这一机制的理解 吸吮刺激对促性腺激素释放激素神经元功能的抑制 提供与灵长类(包括人类)相关的信息， 其中生殖神经内分泌轴调节卵巢 周期性也受到抑制。这些研究与女性的 生殖健康，因为它们将增加我们对 下丘脑导致不孕症的原因并提供新的治疗方法 避孕。资助美国国立卫生研究院HD14643出版物李超，陈平，史密斯 MS急性哺乳刺激诱导神经肽Y的表达 (NPY)在下丘脑背内侧的细胞内，并增加NPY 在弓状核有表达。内分泌学139：1645-1652,1998。 李春，陈平，史密斯女士弓状核神经肽Y(NPY)神经元 核团(ARH)和背内侧核(DMH)。 哺乳，投射到下丘脑室旁核 (PVH)。Reg多肽75-76：93-100,1998。李超、陈平、史密斯女士。 神经肽Y(NPY)和漏斗状多巴胺(TIDA)改变 催乳素在哺乳期的作用。内分泌学140 118-123,1999。 哺乳过程中海马体的阻力 大鼠对N-甲基-D-天冬氨酸(NMDA)的兴奋不是由于 不起作用的受体系统。《脑资源》814：157-163,1998。格罗夫 3？-羟基类固醇脱氢酶(3？-HSD)和信使核糖核酸 在大鼠脑内的分布。在内分泌学会项目中& 摘要第80届年会(6月24-27日在洛杉矶新奥尔良举行 1998)，第493页(摘要#P3-527)。Brogan RS，Kuper J，Duncan JS， 哺乳期间血清瘦素水平为 与代谢排出的乳汁投射缺乏相关性 至血清黄体生成素。在内分泌社会计划中&第80届年会摘要 会议(1998年6月24日至27日在洛杉矶新奥尔良举行)，第349页(摘要 #P2-478)。陈平，Haskell-Luevano C，Cone Rd，Smith MS共同表达 刺鼠相关转录本(ART)和神经肽Y(NPY)在脑组织中的表达 发情周期雌性大鼠下丘脑弓状核的变化 和哺乳期。在内分泌社会计划&摘要第80期 年会(1998年6月24日至27日在洛杉矶新奥尔良举行)，第521页 (摘要#P3-663)。李超，陈平，史密斯女士解剖互动 弓状核神经肽Y神经元之间的相互作用 下丘脑(ARH-NPY)与促性腺激素释放激素(GnRH) 在下丘脑。内分泌学会计划与摘要 第80届年会(1998年6月24日至27日在洛杉矶新奥尔良举行)，第59页 (摘要#或5-5)。李春，陈平，史密斯女士神经肽Y神经元 直接从下丘脑弓状核(ARH-NPY)发出 促肾上腺皮质激素释放激素(CRF)神经元在中脑的投射 室旁核(PVH)。SoC Neurosci abstr 24(1号脚本)：369,1998 (摘要#146.8)。Brogan RS，Grove KL，Smith女士瘦素受体 在哺乳期间的表达。生殖研究学会 58(附录1)：96(摘要#81)。

The reproductive state of lactation, which occurs in all mammals, is associated with an inhibition of reproductive cyclicity and ovulation due to a suppression of gonadotropin releasing hormone (GnRH), the hypothalamic neuroendocrine neurons regulating reproduction. The focus of our studies is to identify the afferent neuronal pathways activated during lactation by the suckling stimulus that are responsible for the suppression of GnRH neuronal function. This past year, we made the following observations 1) Using neuronal tract tracing techniques and confocal microscopy, we have shown that NPY neurons activated by the suckling stimulus project to areas containing GnRH neurons and make contact with GnRH neuronal processes. These results suggest a possible neuronal mechanism by which suckling inhibits GnRH neuronal activity. 2) The large increase in food intake during lactation most likely occurs in response to substances that signal changes in metabolic activit y, such as leptin (a satiety-inducing substance) and agouti-related transcript (ART, induces obesity). During lactation, blood leptin levels are greatly suppressed, whereas ART expression is increased in the hypothalamus. Current studies in the laboratory are examining the relationship between the changes in leptin and ART and the increase in NPY neuronal activity and food intake. In addition, we are exploring possible interactions between the regulation of food intake and of gonadotropin releasing hormone neuronal activity during lactation. It is well established that many causes of infertility are related to changes in energy homeostasis, such as in exercised-induced amenorrhea and anorexia nervosa. An understanding of the mechanisms by which the suckling stimulus imposes an inhibition on GnRH neuronal function provides information that is relevant to primates (including humans), in which the reproductive neuroendocrine axis regulating ovarian cyclicity is also inhibited. These studies have relevance to women's reproductive health as they will increase our understanding of hypothalamic causes of infertility and provide new approaches for contraception. FUNDING NIH HD14643 PUBLICATIONS Li C, Chen P, Smith MS. The acute suckling stimulus induces expression of Neuropeptide Y (NPY) in cells in the dorsomedial hypothalamus and increases NPY expression in the arcuate nucleus. Endocrinology 139:1645-1652, 1998. Li C, Chen P, Smith MS. Neuropeptide Y (NPY) neurons in the arcuate nucleus (ARH) and dorsomedial nucleus (DMH), areas activated during lactation, project to the paraventricular nucleus of the hypothalamus (PVH). Reg Peptides 75-76:93-100, 1998. Li C, Chen P, Smith MS. Neuropeptide Y (NPY) and tuberinfundibular dopamine (TIDA) are altered during lactation role of prolactin. Endocrinology 140 118-123,1999. Grove KL, Smith MS. Resistance of the hippocampus in the lactating rat to N-methyl-D-aspartate (NMDA)-mediated excitation is not due to a nonfunctional receptor system. Brain Res 814:157-163, 1998. Grove KL, Smith MS. 3?-hydroxysteroid dehydrogenase (3? -HSD) and mRNA distribution in the rat brain. In The Endocrine Society Program & Abstracts 80th Annual Meeting (held in New Orleans, LA, June 24-27, 1998), p 493 (abstract #P3-527). Brogan RS, Kuper J, Duncan JS, Trayhurn P, Smith MS. Serum leptin levels during lactation are related to the metabolic drain of milk projection lack of correlation to serum LH. In The Endocrine Society Program & Abstracts 80th Annual Meeting (held in New Orleans, LA, June 24-27, 1998), p 349 (abstract #P2-478). Chen P, Haskell-Luevano C, Cone RD, Smith MS. Coexpression of agouti-related transcript (ART) and neuropeptide Y (NPY) in the hypothalamic arcuate nucleus of female rats during the estrous cycle and lactation. In the Endocrine Society Program & Abstracts 80th Annual Meeting (held in New Orleans, LA, June 24-27, 1998), p 521 (abstract #P3-663). Li C, Chen P, Smith MS. Anatomical interactions between neuropeptide Y neurons from arcuate nucleus of the hypothalamus (ARH-NPY) and the gonadotropin-releasing hormone (GnRH) in the hypothalamus. In The Endocrine Society Program & Abstracts 80th Annual Meeting (held in New Orleans, LA, June 24-27, 1998), p 59 (abstract #OR5-5). Li C, Chen P, Smith MS. Neuropeptide Y neurons from the arcuate nucleus of the hypothalamus (ARH-NPY) directly project to corticotropin releasing hormone (CRF) neurons in the paraventricular nucleus (PVH). Soc Neurosci Abstr 24(pt 1):369, 1998 (abstract #146.8). Brogan RS, Grove KL, Smith MS. Leptin receptor expression during lactation. Society for the Study of Reproduction 58(suppl 1):96 (abstract #81).