SOWER, Stacia A.; University of New Hampshire: Howard Bern Lecture: Insight into the Molecular Evolution of Gonadotropin and its Receptor in the Hormonal Regulation of Reproduction

Gonadotropin-releasing hormone (GnRH) is the central regulator of reproduction in all vertebrates. In response to GnRH, gonadotropins (GTHs) are secreted from the pituitary and stimulate gonadal steroidogenesis and gametogenesis. Lamprey hold a unique position between protochordates and gnathostomes and are the oldest extant lineage of vertebrates, the agnathans. Little has been known about their reproductive pituitary hormones even though lamprey have two GnRHs that have demonstrated functional regulation of the pituitary-gonadal axis. The current studies were undertaken to identify the GTH(s) and its receptor(s) in sea lamprey, Petromyzon marinus, to gain a further understanding of the origin and evolution of reproductive pituitary hormones and their receptors. A sea lamprey preGTH cDNA was cloned in which the GTH&beta consisted of 134 amino-acid residues. Phylogenic analysis of the LH-FSH family showed that lamprey GTH&beta is a clear out-group to vertebrate glycoprotein hormones (LH, FSH, TSH) suggesting that there is a single GTH in agnathans representing an ancestral form of GTH. The cDNA of a functional glycoprotein hormone receptor (LGpH-R1) was also cloned from sea lamprey testes. The high expression of LGpH-R1 in the gonads and the high similarity with gnathostome gonadotropin receptors suggest that lGpH-R1 functions as a receptor for lamprey gonadotropin. The key motifs and characteristics of the identified glycoprotein receptor reveal a mosaic of features common to all other classes of vertebrate glycoprotein hormone receptors. These data will be discussed in relation to the co-evolution of the ligand and its receptor and proposed increased specificities of ligand (TSH, LH, FSH) and receptor interactions in gnathostomes compared to lower specificity of GTH and its receptor in agnathans.