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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 目的：了解 LHRH 脉冲产生的机制及其作用 类固醇对 LHRH 神经元的作用机制。 描述： 下丘脑脉冲性释放 LHRH 对于正常生殖至关重要 功能，但 GnRH 脉冲产生的机制尚不清楚。我们培养 GnRH 源自嗅坑/基板区域的神经元并表征 GnRH 脉冲产生的细胞机制。肽释放的周期性 GnRH 神经元的爆发活动比小鼠 GnRH 神经元慢得多， 尽管猴子 GnRH 神经元的许多特征与那些相似 为小鼠描述。本研究的目的是了解 GnRH 的机制 脉冲产生和类固醇对 GnRH 神经元的作用机制。 进步： 我们取得了三项重要发现。一、灵长类GnRH神经元成熟 其特点是自发同步性的发展依赖于年龄 [Ca2+]i 振荡、脉冲肽释放、GnRH 基因表达增加和 GnRH 基因 5' CpG 丰富区域的去甲基化。二、行动迅速 雌二醇诱导细胞内钙振荡和 GnRH 释放的介导 雌激素受体α和β都没有。相反，它似乎在一定程度上是经过调解的 由 7 次跨膜 G 蛋白偶联受体 GPR30 以及 STX- 敏感受体。第三，GnRH神经元从细胞体释放十肽 和神经过程。这些令人兴奋的发现对于 避孕工具的开发和不孕症的治疗。 本研究使用了 WNPRC 动物服务和化验服务。 出版物： Terasawa, E.、Kurian, J.R.、Guerriero, K.A.、Kenealy, B.P.、Hutz, E.D. 和 Keen, K.L. 关于非人灵长类 GnRH 神经元控制的最新发现。 J。 神经内分泌。 22:630-638，2010 年。PMID：20456608，PMCID：PMC2908205。 Kurian J.R.、Keen, K.L. 和 Terasawa, E. 2010 表观遗传变化与 体外灵长类 GnRH 神经元成熟。内分泌学 151：5359-5368。 PMID： 20861233，PMCID：PMC2954729。