Adams Bruce A, Tello Javier A, Erchegyi Judit, Warby Carol, Hong Doley J, Akinsanya Karen O, Mackie George O, Vale Wylie, Rivier Jean E, Sherwood Nancy M
Department of Biology, University of Victoria, Victoria, British Columbia, Canada V8W 3N5.
Endocrinology. 2003 May;144(5):1907-19. doi: 10.1210/en.2002-0216.
GnRH is the key regulator of the reproductive axis in vertebrates, but little is known about GnRH before the origin of vertebrates. We have identified two genes encoding GnRH in a protochordate, Ciona intestinalis, thought to be related to the ancestral animal that gave rise to vertebrates. Each gene, Ci-gnrh1 and Ci-gnrh2, encodes in tandem three GnRH peptides, each of which is unique compared with known forms. Ci-gnrh1 encodes three peptides and contains no introns, whereas Ci-gnrh2 encodes three more peptides but has two introns. This is the first report in which more than one GnRH peptide is encoded on a single gene. The Ciona genes reveal consensus promoter elements that are conserved compared with human GNRH1. Both tunicate genes are expressed as mRNA early and throughout development, measured at the stages of four-cell, gastrulation, tail release, and tail resorption. In a closely related tunicate species, Ciona savignyi, we used in silico analysis to identify two similar genes encoding six peptides, only one of which is unique compared with C. intestinalis. Immunohistochemistry showed that at least one GnRH peptide was in the nerve net that surrounds the dorsal strand. Synthetic forms of the seven novel tunicate peptides induced release of gametes in adult tunicates. In contrast, the peptides did not activate the human GnRH-I receptor or cause release of LH in a rat pituitary cell assay. These data provide insight into the structural evolution of the GnRH peptides and their genes and show a functional role for GnRH in tunicate spawning.
促性腺激素释放激素（GnRH）是脊椎动物生殖轴的关键调节因子，但在脊椎动物起源之前，人们对GnRH了解甚少。我们在一种原索动物——玻璃海鞘中鉴定出了两个编码GnRH的基因，玻璃海鞘被认为与脊椎动物的祖先动物有关。每个基因，即Ci-gnrh1和Ci-gnrh2，串联编码三种GnRH肽，与已知形式相比，每种肽都是独特的。Ci-gnrh1编码三种肽且不含内含子，而Ci-gnrh2编码另外三种肽但有两个内含子。这是首次报道单个基因编码不止一种GnRH肽。玻璃海鞘的基因揭示了与人类GNRH1相比保守的共有启动子元件。在四细胞期、原肠胚形成期、尾部释放期和尾部吸收期等阶段进行检测，发现这两种被囊动物基因在发育早期及整个发育过程中均以mRNA形式表达。在一种亲缘关系密切的被囊动物物种——萨氏玻璃海鞘中，我们通过计算机分析鉴定出两个编码六种肽的相似基因，与玻璃海鞘相比，其中只有一种是独特的。免疫组织化学显示，至少有一种GnRH肽存在于围绕背索的神经网中。七种新型被囊动物肽的合成形式诱导成年被囊动物释放配子。相比之下，在大鼠垂体细胞试验中，这些肽并未激活人类GnRH-I受体或导致促黄体生成素（LH）释放。这些数据为GnRH肽及其基因的结构进化提供了见解，并表明GnRH在被囊动物产卵中具有功能性作用。
