CONTROL OF GONADOTROPIN SECRETION DURING LACTATION

哺乳期哺乳的生殖状态，发生在所有哺乳动物中， 与生殖周期的抑制有关， 促性腺激素释放激素抑制排卵 （GnRH），下丘脑神经内分泌神经元调节 生殖 我们研究的重点是确定传入神经 哺乳期哺乳刺激激活的神经通路 负责抑制GnRH神经元功能。 在过去的一年里，我们做了以下观察：1）使用神经元 束跟踪技术和共聚焦显微镜，我们已经表明， 哺乳刺激激活的NPY神经元投射到 含有GnRH神经元并与GnRH神经元过程接触。 这些结果表明，哺乳可能是一种神经机制， 抑制GnRH神经元活性。 2)食物摄入量的大幅增加 在哺乳期最有可能发生的反应， 代谢活动的信号变化，如瘦素（a 饱腹感诱导物质）和刺豚鼠相关转录物（ART， 诱发肥胖症）。 在哺乳期，血液中的瘦素水平大大降低， 抑制，而ART表达在下丘脑中增加。 目前实验室的研究正在研究 瘦素和ART的变化与NPY神经元的增加之间 活动和食物摄入。 此外，我们正在探索可能的 摄食调节和促性腺激素调节之间的相互作用 在哺乳期间释放激素神经元活动。 公 许多不孕症的原因都与 能量稳态，如运动诱发的闭经， 神经性厌食症 了解这些机制， 哺乳刺激对GnRH神经元功能产生抑制作用 提供与灵长类动物（包括人类）相关的信息， 其中生殖神经内分泌轴调节卵巢 循环性也受到抑制。 这些研究与妇女的 生殖健康，因为它们将增加我们对 下丘脑原因不孕症，并提供新的方法， 避孕。 资助NIH HD 14643出版物Li C，Chen P，Smith 女士 急性吸吮刺激诱导神经肽Y的表达 (NPY)在下丘脑背内侧的细胞中， 表达于弓状核。 内分泌学139：1645-1652，1998年。 李春，陈平，史密斯，神经肽Y（NPY）神经元在弓状核中的表达 核（ARH）和背内侧核（DMH）， 泌乳，投射到下丘脑室旁核 （PVH）。 Reg Peptides 75-76：93-100，1998. Li C，Chen P，Smith MS. 神经肽Y（NPY）和结节漏斗多巴胺（TIDA）改变 泌乳期间催乳素的作用。 内分泌学140 118- 123，1999。 格罗夫KL，史密斯MS。泌乳期海马的阻力 大鼠对N-甲基-D-天冬氨酸（NMDA）介导的兴奋不是由于 非功能性受体系统 脑研究814：157-163，1998年。 格罗夫 史密斯女士3？羟类固醇脱氢酶（3？ -HSD）和mRNA 分布在大鼠脑中。 在内分泌学会计划& 摘要第80届年会（6月24日至27日在路易斯安那州新奥尔良举行， 1998），第493页（摘要#P3-527）。 Brogan RS，Kuper J，邓肯JS， Trayhurn P，Smith MS.泌乳期血清瘦素水平 与代谢排泄有关的乳汁投影缺乏相关性 血清LH。 在内分泌学会计划和摘要第80届年度 会议（1998年6月24-27日在路易斯安那州新奥尔良举行），第349页（摘要 #P2-478）。 Chen P，Haskell-Luevano C，Cone RD，Smith MS.共表达 的刺豚鼠相关转录本（ART）和神经肽Y（NPY）在 雌性大鼠动情周期中下丘脑弓状核的变化 和哺乳期。 在内分泌学会计划和摘要80日 年度会议（1998年6月24日至27日在路易斯安那州新奥尔良举行），第521页 （摘要#P3-663）。 Li C，Chen P，Smith MS.解剖学相互作用 弓状核的神经肽Y神经元之间 下丘脑（ARH-NPY）和促性腺激素释放激素（GnRH） 在下丘脑 在内分泌学会计划和摘要 第80届年会（1998年6月24日至27日在路易斯安那州新奥尔良举行），第59页 （摘要#OR5-5）。 李春，陈平，史密斯，神经肽Y神经元 从下丘脑弓状核（ARH-NPY）直接 投射到皮层促肾上腺皮质激素释放激素（CRF）神经元 室旁核（PVH）。 Soc Neurosci Abstr 24（pt 1）：369，1998 （摘要#146.8）。 Brogan RS，格罗夫KL，Smith MS.瘦素受体 在哺乳期表达。 生殖研究学会 58（增刊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).