Minireview: GnRH and GnRH Receptor Genes in the Human Genome

Four different GnRHs and one GnRH receptor are reported to be expressed in various mammals, whereas 13 GnRHs and numerous GnRH receptors have been identified in various nonmammalian vertebrates. The nucleotide sequencing of the human genome provided the opportunity to determine which of these peptides and receptors might be expressed in primates. Of the four GnRHs reportedly expressed in mammals, only GnRH I (mammalian GnRH) and GnRH II (chicken GnRH II) genes were identified in the human genome. Three GnRH receptor or receptor-like genes were identified: 1) the well-established GnRH I receptor gene located on chromosome 4; 2) an apparent GnRH II receptor gene located on chromosome 1, and; 3) a sterile GnRH II receptor-like homolog gene on chromosome 14. A cDNA cloned from monkey RNA that was 96% identical with the putative human GnRH receptor type II gene encoded a 379-amino acid G protein-coupled/7-transmembrane receptor having a C-terminal cytoplasmic tail. The experimentally expressed GnRH II receptor was functional with and specific for GnRH II, and, unlike the GnRH I receptor, desensitized to continuous GnRH treatment. GnRH II receptor mRNA is expressed ubiquitously in human tissues. Significant questions remain about the potential functions of the primate GnRH II receptor such as regulation of gonadotropin secretion, female sexual behavior, and tumor cell growth; also, about whether it is expressed as a full-length, functional gene transcript in humans.