Molecular and Functional Investigations of Gonadotropin and Gonadotropin Releasing Hormone in Lamprey Reproduction

[9722765]康顿：这个提案将研究一种古老的鱼类——七鳃鳗的大脑和脑垂体对繁殖的控制。七鳃鳗很重要，因为它们是最古老的脊椎动物——无颌鱼——的成员，并提出了关于进化的有趣问题。本实验室主要研究七鳃鳗脑-垂体-性腺轴中两种脑激素的结构和功能。七鳃鳗的两种脑激素，促性腺激素释放激素（GnRH- I和GnRH- iii）的主要结构已被确定。这些信息与免疫细胞化学和生理学研究相结合，为大脑对七鳃鳗垂体-性腺轴的调节作用提供了强有力的证据。此外，七鳃鳗是第一个明确证明GnRH分子作为神经激素介导垂体-性腺轴的双重作用的脊椎动物。然而，关于GnRH在生殖过程中的作用的研究一直受到缺乏确定的促性腺激素的阻碍，这种促性腺激素可用于测定垂体对GnRH的反应性。七鳃鳗垂体促性腺激素（GTH）的纯化和鉴定是研究七鳃鳗下丘脑-垂体-性腺关系的关键。因此，在七鳃鳗中需要识别GTH并验证下丘脑影响垂体性腺轴的方式，并且是本项目的一部分。实验将结合多种方法来进一步定义Agnathans中大脑和垂体的关系。目前正在进行的和拟进行的研究主要集中在七鳃鳗中GnRH的分子、生化和功能研究，以验证从大脑释放的多种形式的GnRH影响调节性腺功能的促性腺激素样分子的合成和分泌的假设。这些对七鳃鳗的研究结果将更好地理解从无脊椎动物到后来进化的脊椎动物的分子进化。这项研究旨在观察七鳃鳗体内是否存在从下丘脑到垂体和性腺的调节。七鳃鳗属于最古老的脊椎动物谱系之一，被用来研究各种脊椎动物信号系统的起源。本实验室已经确定并测序了七鳃鳗下丘脑的促性腺激素释放激素，现在想要确定垂体对GnRH的反应释放激素。环境因素对这一激素通路的影响也将被确定。这项研究将有助于更好地理解生殖系统的分子进化。＊＊＊

9722765 Condon This proposal will investigate the control of reproduction by the brain and pituitary in an ancient fish, the lamprey. Lampreys are important because they are members of the oldest lineage of vertebrates, the Agnathans or jawless fish, and raise interesting questions on evolution. This laboratory has focused on the structure and function of two brain hormones involved in the brain- pituitary gonadal axis in lampreys. The primary structures of two brain hormones, gonadotropin-releasing hormone (GnRH- I and GnRH-III) have been determined in lampreys. This information combined with immunocytochemical and physiological studies provides strong evidence for the regulatory influence of the brain on the pituitary-gonadal axis in lampreys. In addition, lampreys are the first vertebrates to clearly demonstrate a dual role for GnRH molecules as neurohormones mediating the pituitary-gonadal axis. However, the investigations on the role of GnRHs in reproductive processes have been impeded by the lack of an identified gonadotropin that could be used in assays as a measure of pituitary responsiveness to GnRH. The purification and identification of lamprey pituitary gonadotropin, GTH, is critical to examine the hypothalamic- pituitary-gonadal relations in lampreys. Thus identification of GTH and verification of the ways in which the hypothalamus affects the pituitary gonadal axis are needed in the lamprey, and are part of this project. The experiments will incorporate a variety of approaches to further define the relationship of the brain and pituitary in Agnathans. The ongoing and proposed studies are focused on molecular, biochemical and functional studies of GnRHs in lampreys to test the hypothesis that multiple forms of GnRH released from the brain influence the synthesis and secretion of a gonadotropin-like molecule which regulated the function of the gonads. Results fsrom these studies in lampreys will provide better understanding of the molecular evolution from invertebrates to later evolved vertebrates. %%% This research is looking to see if there is regulation from the hypothalamus to the pituitary and the gonads in the lamprey. The lamprey belongs to one of the oldest lineage's of vertebrates and is used to look at the origin of various vertebrate signaling systems. This laboratory has identified and sequenced the gonadotropin releasing hormone from the hypothalamus of the lamprey, and now wants to identify the hormone released from the pituitary in response to GnRH. Also the effects of environmental factors on this hormonal pathway will be determined. This research will provide a better understanding of molecular evolution of the reproductive system. ***