GENES CONTROLLING PUBERTY ONSET

控制青春期开始的基因

• 批准号: 8173078
• 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/8173078
• 关键词: Agonist; Animals; Behavioral; Biological Assay; Brain; Computer Retrieval of Information on Scientific Projects Database; Development; Disease; Estrogens; Female; Frequencies; Funding; Genes; Gonadotropins; Grant; Institution; KISS1R gene; Measures; Methods; Microdialysis; Ovarian; Peptides; Physiologic pulse; Physiological; Play; Puberty; Publications; Regulation; Research; Research Personnel; Resources; Role; Services; Source; Time; United States National Institutes of Health; kisspeptin; median eminence; prepuberty; response

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 investigate genes controlling the timing of puberty. Understanding the mechanism of puberty in the brain is important, as some diseases and behavioral disturbances occur in association with puberty. In this study the role of kisspeptin in the pubertal increase in LHRH release was examined. The results suggest that kisspeptin-54 release in the stalk-median eminence measured by a microdialysis method was pulsatile and mean kisspeptin-54 levels and pulse frequency, but not pulse amplitude, increased at the onset of puberty. Moreover, the pubertal increase in kisspeptin-54 release was independent from the pubertal changes in circulating ovarian estrogen, as the pubertal increase in kisspeptin-54 release was also observed in ovariectomized females. Finally, developmental changes in GPR54 sensitivity to KP were examined by assessing the LHRH response to a KP agonist and antagonist, KP-10 and peptide 234, respectively. Preliminary results suggest that the LHRH response to neither KP-10 nor peptide 234 was different between prepubertal and pubertal groups, indicating that GPR54 sensitivity does not undergo developmental changes. Collectively, the results are consistent with the hypothesis that kisspeptin plays a role in puberty. This research used WNPRC Animal Services and Assay Services. PUBLICATION: Roseweir, A.K., Kauffman, A.S., Smith, J.T., Guerriero, K.A., Morgan, K., Pielecka-Fortuna, J., Pineda, R., Gottsch, M.L., Tena-Sempere, M., Moenter, S.M., Terasawa, E., Clarke, I.J., Steiner, R.A., and Millar, R.P. Discovery of potent kisspeptin antagonists delineate physiological mechanisms of gonadotropin regulation. J. Neurosci. 29:3920-3929, 2009. PMID: 19321788

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：研究控制青春期时间的基因。 了解青春期大脑的机制很重要，因为一些疾病和行为障碍的发生与青春期有关。 在这项研究中，检查了 Kisspeptin 在青春期 LHRH 释放增加中的作用。结果表明，通过微透析方法测量的茎中隆起中的 Kisspeptin-54 释放是脉动的，并且平均 Kisspeptin-54 水平和脉冲频率（但不是脉冲幅度）在青春期开始时增加。此外，青春期 Kisspeptin-54 释放的增加与青春期循环卵巢雌激素的变化无关，因为在卵巢切除的女性中也观察到青春期 Kisspeptin-54 释放的增加。最后，通过评估 LHRH 分别对 KP 激动剂和拮抗剂 KP-10 和肽 234 的反应来检查 GPR54 对 KP 敏感性的发育变化。 初步结果表明，LHRH 对 KP-10 和肽 234 的反应在青春期前和青春期组之间没有差异，表明 GPR54 敏感性不会发生发育变化。总的来说，这些结果与 Kisspeptin 在青春期发挥作用的假设是一致的。 本研究使用了 WNPRC 动物服务和化验服务。 发布： Roseweir, A.K.、Kauffman, A.S.、Smith, J.T.、Guerriero, K.A.、Morgan, K.、Pieecka-Fortuna, J.、Pineda, R.、Gottsch, M.L.、Tena-Sempere, M.、Moenter, S.M.、Terasawa, E.、Clarke, I.J.、Steiner, R.A. 和 Millar， R.P. 强效 Kisspeptin 拮抗剂的发现描述了促性腺激素调节的生理机制。 J.神经科学。 29:3920-3929, 2009. PMID: 19321788