Molecular characterisation of the gonadotropin-releasing hormone receptor gene

Abstract

The gonadotropin-releasing hormone (GnRH) receptor is a plasma membrane associated receptor and a member of the GTP-binding protein coupled receptor family. The interaction of GnRH and its receptor is a critical event in the endocrine control of reproduction. We have recently isolated the gene encoding the human pituitary GnRH receptor. The genomic clones obtained encompassed the full-length coding region and substantial portions of the 5′ and 3′ non-coding regions. Analysis of the clones revealed that the gene contains three exons and two introns which are distributed over 18.9 kb. Five putative promoters and transcription initiation sites have been identified in the 5′ end of the gene. Several consensus cis-acting regulatory sequences, such as sites for PEA-3, AP-1 and Pit-1, were identified within the 5′ flanking region. At the 3′ end of the gene, five classical polyadenylation signals were found scattered over a region of 800 bp. The mouse, sheep and rat GnRH receptor genes have also been characterised partially; these genes show similar structure and identical exon-intron splicing sites to the human GnRH receptor gene. However, the transcription start sites of the mouse and rat GnRH receptor genes are much closer to the translation start site when compared with the human GnRH receptor gene and multiple TATA boxes were not found in the promoter region of the mouse and rat GnRH receptor genes. On the other hand, initial characterisation of the ovine GnRH receptor gene indicates that, like the human gene, it contains multiple transcription initiation sites and far more 5′ untranslated region than the murine gene. Characterisation of the GnRH receptor gene provides the basis for further study of the complex mechanisms involved in the transcriptional regulation of GnRH receptor gene expression.