RFamide Influence on Gonadal Activity

RFamide 对性腺活性的影响

• 批准号: 0641188
• 负责人: George Bentley
• 金额: $ 47.22万
• 依托单位: University of California-Berkeley
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0641188&HistoricalAwards=false
• 关键词: RFamide; Influence; Gonadal; Activity

Neuropeptide control of gonadotropin secretion at the level of the anterior pituitary gland is primarily through the stimulatory action of the hypothalamic decapeptide, gonadotropin-releasing hormone (GnRH), which was originally isolated from mammals and subsequently from non-mammals including birds. Although studies of the different forms of GnRH and its receptors have revealed a wealth of information as to their function, an inhibitory hypothalamic neuropeptide for gonadotropin release has, until recently, remained unknown in any vertebrate. In 2000, a novel RFamide neuropeptide was found specifically to inhibit gonadotropin release in quail (Tsutsui et al., 2000). This peptide has now been named gonadotropin-inhibitory hormone (GnIH). A gonadotropin inhibitory system is an intriguing concept and provides an unprecedented opportunity to study the regulation of reproduction from an entirely novel standpoint. Recent findings in the PI's laboratory indicate that in addition to synthesis in the brain, GnIH is also synthesized in male and female gonads of songbirds. In addition, the receptor for GnIH is expressed in the gonads of both sexes. Expression of both GnIH and its receptor in the gonads provides the framework for an additional level of control of the reproductive system in response to environmental cues. Thus, it would be beneficial to the field of vertebrate reproductive biology in general to understand why GnIH and its receptor are expressed in the gonads. At present, almost nothing is known about this hormone system in the gonads. This project focuses on GnIH and its receptor in avian gonads in order to provide solid baseline data for further studies on the interactions of the hypothalamo-pituitary-gonadal axis. Without fundamental data on gonadal GnIH, its location and function, interpretations about brain-gonad interactions cannot be made correctly. The broader impacts of this research include training of graduate students in laboratories in different countries, undergraduate participation in research and scientific meetings, and inclusion of deserving undergraduates as authors on publications. Furthermore, the intellectual merit of the results obtained includes advancement our understanding of a novel hormone system which influences reproduction in all vertebrates studied to date. A great deal is known about GnIH in the brain, but how neural GnIH interacts with gonadal GnIH to time reproductive effort is unknown. This project will provide solid data upon which a deeper understanding of this newly-identified hormone system can be built.

垂体前叶水平的促性腺激素分泌的神经肽控制主要是通过下丘脑十肽，促性腺激素释放激素（GnRH）的刺激作用，该激素最初从哺乳动物中分离出来，随后从包括鸟类在内的非哺乳动物中分离出来。尽管对不同形式的GnRH及其受体的研究已经揭示了其功能的丰富信息，但直到最近，在任何脊椎动物中仍未发现促性腺激素释放的抑制性下丘脑神经肽。2000年，一种新的RFamide神经肽被发现能特异性抑制鹌鹑的促性腺激素释放（Tsutsui et al., 2000）。这种肽现在被命名为促性腺激素抑制激素（GnIH）。促性腺激素抑制系统是一个有趣的概念，提供了一个前所未有的机会，从一个全新的角度来研究生殖调节。PI实验室最近的发现表明，GnIH除了在大脑中合成外，还在鸣禽的雄性和雌性性腺中合成。此外，GnIH受体在两性性腺中均有表达。GnIH及其受体在性腺中的表达为生殖系统响应环境信号的额外控制水平提供了框架。因此，了解GnIH及其受体为何在性腺中表达，将有利于脊椎动物生殖生物学的研究。目前，人们对性腺中的这种激素系统几乎一无所知。本项目重点研究GnIH及其受体在禽类性腺中的作用，为进一步研究下丘脑-垂体-性腺轴的相互作用提供坚实的基线数据。如果没有关于性腺GnIH及其位置和功能的基本数据，就无法正确解释脑-性腺相互作用。这项研究的更广泛的影响包括在不同国家的实验室培养研究生，本科生参与研究和科学会议，以及将合格的本科生纳入出版物的作者。此外，所获得的结果的智力价值包括推进我们对一种影响迄今为止所研究的所有脊椎动物生殖的新型激素系统的理解。关于大脑中的GnIH，我们已经知道了很多，但是神经GnIH是如何与性腺GnIH相互作用来决定生殖努力的时间的，我们还不得而知。该项目将提供可靠的数据，在此基础上可以更深入地了解这种新发现的激素系统。