Molecular Biology of Gonadotropin-Releasing Hormone (GnRH)-I, GnRH-II, and Their Receptors in Humans
Chi Keung Cheng and
Peter C. K. Leung
Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada V6H 3V5
Correspondence: Address all correspondence and requests for reprints to: Peter C. K. Leung, Ph.D., Department of Obstetrics and Gynecology, University of British Columbia, 2H30-4490 Oak Street, British Columbia Women’s Hospital, Vancouver, British Columbia, Canada V6H 3V5. E-mail: peleung{at}interchange.ubc.ca
In human beings, two forms of GnRH, termed GnRH-I and GnRH-II,encoded by separate genes have been identified. Although thesehormones share comparable cDNA and genomic structures, theirtissue distribution and regulation of gene expression are significantlydissimilar. The actions of GnRH are mediated by the GnRH receptor,which belongs to a member of the rhodopsin-like G protein-coupledreceptor superfamily. However, to date, only one conventionalGnRH receptor subtype (type I GnRH receptor) uniquely lackinga carboxyl-terminal tail has been found in the human body. Studieson the transcriptional regulation of the human GnRH receptorgene have indicated that tissue-specific gene expression ismediated by differential promoter usage in various cell types.Functionally, there is growing evidence showing that both GnRH-Iand GnRH-II are potentially important autocrine and/or paracrineregulators in some extrapituitary compartments. Recent cloningof a second GnRH receptor subtype (type II GnRH receptor) innonhuman primates revealed that it is structurally and functionallydistinct from the mammalian type I receptor. However, the humantype II receptor gene homolog carries a frameshift and a prematurestop codon, suggesting that a full-length type II receptor doesnot exist in humans.
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