LHRH PULSE GENERATION AND STEROID FEEDBACK

LHRH 脉冲生成和类固醇反馈

• 批准号: 8173067
• 负责人: Ei Terasawa-Grilley
• 金额: $ 3.1万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173067
• 关键词: Agonist; Animals; Biological Assay; Calcium Oscillations; Characteristics; Computer Retrieval of Information on Scientific Projects Database; Contraceptive Agents; Development; Estradiol; Estrogens; Feedback; Frequencies; Funding; G-Protein-Coupled Receptors; Generations; Grant; Hypothalamic structure; Infertility; Institution; Mediating; Monkeys; Mus; Neurons; Peptides; Periodicity; Physiologic pulse; Primates; Research; Research Personnel; Resources; Role; Services; Small Interfering RNA; Source; Steroids; United States National Institutes of Health; receptor; reproductive function; response; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To understand the mechanism of LHRH pulse generation and the mechanism of steroid action on LHRH neurons. Pulsatile release of LHRH from the hypothalamus is essential for normal reproductive function, yet the mechanism of LHRH pulse generation is unclear. We cultured LHRH neurons originating from the olfactory pit/placode region and characterized the cellular mechanism of LHRH pulse generation. The periodicity of peptide release and bursting activity of LHRH neurons were much slower than mouse LHRH neurons, although many characteristics in monkey LHRH neurons are similar to those described for mice. The aim of this study is to understand the mechanism of LHRH pulse generation and the mechanism of steroid action on LHRH neurons. Recently, we found that LHRH neurons respond to estradiol with a short latency (within a minute), stimulating the frequency of firing activity and intracellular calcium oscillations, and LHRH release. This rapid action of estradiol appears to be, in part, mediated by the 7-transmembrane receptor, GPR30, as LHRH neurons treated with siRNA for GPR30 do not respond to estradiol, and the GPR30 agonist G1 causes a response similar to estradiol. Moreover, the rapid action of estradiol through GPR30 is dissimilar to the rapid action caused by the synthetic estrogenic substance, STX. 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: Noel, S.D., Keen, K.L., Baumann, D.I., Filardo, E.J., and Terasawa, E. Involvement of G-protein coupled receptor 30 (GPR30) in rapid action of estrogen in primate LHRH neurons. Mol. Endocrinol. 23: 349-359, 2009. PMID: 19131510 Terasawa, E., Noel, S.D., and Keen, K.L. Rapid action of estrogen in LHRH neurons: The role of GPR30. J. Neuroendocrinol. 21: 316-321, 2009. PMID: 19207808

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 目的：了解LHRH脉冲产生的机制以及类固醇对LHRH神经元的作用机制。 下丘脑脉冲性释放 LHRH 对于正常生殖功能至关重要，但 LHRH 脉冲产生的机制尚不清楚。我们培养了源自嗅坑/基板区域的 LHRH 神经元，并表征了 LHRH 脉冲产生的细胞机制。尽管猴 LHRH 神经元的许多特征与小鼠的特征相似，但 LHRH 神经元的肽释放周期和爆发活性比小鼠 LHRH 神经元慢得多。本研究的目的是了解 LHRH 脉冲产生的机制以及类固醇对 LHRH 神经元的作用机制。 最近，我们发现LHRH神经元对雌二醇的反应潜伏期很短（一分钟内），刺激放电活动的频率和细胞内钙振荡，以及LHRH释放。雌二醇的这种快速作用似乎部分是由 7 次跨膜受体 GPR30 介导的，因为用 GPR30 的 siRNA 处理的 LHRH 神经元不会对雌二醇产生反应，而 GPR30 激动剂 G1 会引起与雌二醇类似的反应。此外，雌二醇通过GPR30的快速作用与合成雌激素物质STX引起的快速作用不同。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极其重要。 本研究使用了 WNPRC 动物服务和化验服务。 出版物： Noel, S.D.、Keen, K.L.、Baumann, D.I.、Filardo, E.J. 和 Terasawa, E. G 蛋白偶联受体 30 (GPR30) 参与灵长类 LHRH 神经元雌激素的快速作用。摩尔。内分泌。 23：349-359，2009。PMID：19131510 Terasawa, E.、Noel, S.D. 和 Keen, K.L.雌激素在 LHRH 神经元中的快速作用：GPR30 的作用。 J.神经内分泌。 21：316-321，2009。PMID：19207808