LHRH PULSE GENERATION AND STEROID FEEDBACK

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 目的：了解LHRH脉冲产生的机制及类固醇激素对LHRH神经元的作用机制。 下丘脑脉冲性释放LHRH对正常生殖功能至关重要，但LHRH脉冲产生的机制尚不清楚。我们培养的LHRH神经元起源于嗅窝/基板区域，其特征在于LHRH脉冲产生的细胞机制。LHRH神经元的肽释放和爆发活性的周期性比小鼠LHRH神经元慢得多，尽管猴LHRH神经元的许多特征与小鼠的相似。本研究的目的是了解LHRH脉冲产生的机制和类固醇对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具有短的潜伏期（在一分钟内），刺激放电活动和细胞内钙振荡的频率，以及LHRH的释放。雌二醇的这种快速作用似乎部分地由7-跨膜受体GPR 30介导，因为用针对GPR 30的siRNA处理的LHRH神经元对雌二醇没有反应，并且GPR 30激动剂G1引起与雌二醇类似的反应。此外，雌二醇通过GPR 30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非常重要。 本研究使用WNPRC Animal Services和Assay Services。 出版物： 诺埃尔，S.D.，Keen，K.L.，鲍曼，D.I.，Filardo，E.J.， 和Terasawa，E. G蛋白偶联受体30（GPR 30）参与灵长类LHRH神经元雌激素的快速作用。摩尔年. 23：349-359，2009. PMID：19131510 Terasawa，E.，诺埃尔，S.D.，和Keen，K.L.雌激素在LHRH神经元中的快速作用：GPR 30的作用。J. Neuroendocrinol. 21：316-321，2009. PMID：19207808

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