Abstract
In vertebrates, GnRH binds to its receptor and stimulates predominantly G(q/11)-mediated signal transduction in gonadotropes. However, little is known about the GnRH receptor and its signaling pathway in the protochordate tunicates (sea squirts) a group that arose before the vertebrates and lacks both a pituitary gland and sex steroids. We have recently identified two genes in Ciona intestinalis that each code for three GnRH peptides. The structure of the six peptides is closely related to vertebrates GnRHs and each is bioactive in the C. intestinalis reproductive system. The genes for the ligands are expressed in the neural complex as well as peripheral tissues including the gonads and intestine. Furthermore, we identified in the genome and characterized four GnRH receptors that have a wide tissue distribution, including heart, neural complex, intestine, and gonads. The four GnRH receptors were all transcribed into messenger RNA, and three were biologically active in our COS-7 cell assays; work on the fourth receptor is in progress. Three C. intestinalis receptors almost exclusively activated the cAMP pathway. In contrast, only GnRH receptor 1 activated inositol phosphate turnover in response to one of the native C. intestinalis GnRHs. In summary, our current understanding of GnRH function in C. intestinalis is a model of a decentralized GnRH regulatory axis in which the ligand and receptor structures have been generally conserved but may have shifted the dominant signaling pathways that are activated.
Published Version
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