LHRH PULSE GENERATION AND STEROID FEEDBACK

LHRH 脉冲产生和类固醇反馈

• 批准号: 8358195
• 负责人: Ei Terasawa-Grilley
• 金额: $ 15.64万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358195
• 关键词: Animals; Biological Assay; Calcium Oscillations; Characteristics; Contraceptive Agents; Development; Endocrinology; Epigenetic Process; Estradiol; Estrogen Receptor alpha; Feedback; Funding; G-Protein-Coupled Receptors; Gene Expression; Generations; Genes; Grant; Hypothalamic structure; In Vitro; Infertility; Mediating; Monkeys; Mus; National Center for Research Resources; Neurons; Peptides; Periodicity; Physiologic pulse; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Services; Source; Steroids; United States National Institutes of Health; Wisconsin; age related; cost; demethylation; neuronal cell body; nonhuman primate; receptor; reproductive function; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Objective: To understand the mechanism of LHRH pulse generation and the mechanism of steroid action on LHRH neurons. DESCRIPTION: Pulsatile release of LHRH from the hypothalamus is essential for normal reproductive function, yet the mechanism of GnRH pulse generation is unclear. We cultured GnRH neurons originating from the olfactory pit/placode region and characterized the cellular mechanism of GnRH pulse generation. The periodicity of peptide release and bursting activity of GnRH neurons were much slower than mouse GnRH neurons, although many characteristics in monkey GnRH neurons are similar to those described for mice. The aim of this study is to understand the mechanism of GnRH pulse generation and the mechanism of steroid action on GnRH neurons. PROGRESS: We have made three important discoveries. First, primate GnRH neuronal maturation is characterized by age-dependent development of spontaneous synchronizing [Ca2+]i oscillations, pulsatile peptide release, increased GnRH gene expression and demethylation of a 5' CpG rich region of the GnRH gene. Second, rapid action of estradiol inducing intracellular calcium oscillations and GnRH release is mediated by neither estrogen receptor alpha nor beta. Rather, it appears to be, in part, mediated by the 7-transmembrane G-protein coupled receptor, GPR30 as well as a STX- sensitive receptor. Third, GnRH neurons releases the decapeptide from the cell body and neuroprocesses. These exciting findings are extremely important for the development of contraceptive tools and treatment of infertility. This research used WNPRC Animal Services and Assay Services. PUBLICATIONS: Terasawa, E., Kurian, J.R., Guerriero, K.A., Kenealy, B.P., Hutz, E.D., and Keen, K.L. Recent discoveries on the control of GnRH neurons in nonhuman primates. J. Neuroendocrinol. 22:630-638, 2010. PMID: 20456608, PMCID: PMC2908205. Kurian J.R., Keen, K.L., and Terasawa, E. 2010 Epigenetic changes coincide with in vitro primate GnRH neuronal maturation. Endocrinology 151:5359-5368. PMID: 20861233, PMCID: PMC2954729.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 目的：了解促黄体生成素(LHRH)脉冲的产生机制和作用机制。 类固醇对LHRH神经元的作用机制。 说明： 下丘脑LHRH的脉动性释放对正常生殖是必不可少的 然而，GnRH脉冲产生的机制尚不清楚。我们培养了促性腺激素释放激素 起源于嗅窝/胎盘区域的神经元 促性腺激素释放激素脉冲产生的细胞机制。多肽释放的周期性和 GnRH神经元的爆发性活动比小鼠GnRH神经元慢得多， 尽管猴子促性腺激素释放激素神经元的许多特征与 为老鼠描述的。本研究旨在了解促性腺激素释放激素的作用机制。 脉冲产生和类固醇对GnRH神经元的作用机制。 进度： 我们有三个重要的发现。首先，灵长类GnRH神经元的成熟 以年龄相关的自发同步化发展为特征 [Ca~(2+)]i振荡、脉冲性多肽释放、GnRH基因表达增加和 GnRH基因5‘CpG富集区去甲基化。第二，迅速采取行动 雌激素诱导细胞内钙振荡和促性腺激素释放激素是通过 雌激素受体既不是α也不是β。相反，它似乎在一定程度上是通过 通过7-跨膜G蛋白偶联受体GPR30和STX- 敏感的受体。第三，促性腺激素释放激素神经元从细胞体释放十肽 和神经过程。这些令人振奋的发现对于 避孕工具的开发和不孕症的治疗。 这项研究使用了WNPRC动物服务和化验服务。 出版物： 首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容 非人灵长类GnRH神经元控制的最新发现。J. 神经内分泌。2010年22：630-638。PMID：20456608，PMC2908205。 Kurian J.R.，Ken，K.L.和Terasawa，E.2010年的表观遗传学变化与 灵长类促性腺激素释放激素神经元的体外成熟。内分泌科151：5359-5368。PMID： 20861233，PMCID：PMC2954729。