The function of the Gonadotropin Releasing Hormone (GnRH) gene is central to the reproductive capability of mammalian organisms. At the cellular level many factors may act to regulate the production of the GnRH decapeptide via effects on transcription, translation and post-translational events. The structures of the mRNA and genomic locus encoding the GnRH precursor in the rat and human have been described. Further work revealed that the DNA in the rat which encodes the GnRH precursor on one DNA strand, also encodes a distinct gene, SH, on the opposite DNA strand. The SH and GnRH genes share significance exonic sequences and the RNAs transcribed from either strand show distinct but overlapping patterns of tissue and cellular specificity. The major goal of the research proposed here is to more thoroughly characterize the GnRH:SH gene locus and examine the functional relationship between the GnRH and SH gene products. First, will be to localize the promoter elements present on both strands of the GnRH:SH gene by mapping transcriptional initiation sites, and by assaying the ability of implicated genomic sequences to drive expression of reporter genes. Second, will be to determine if the SH RNAs produce proteins in vivo. Third, will be to determine whether there are cells which co-express the GnRH and SH genes. Fourth, will be to examine the consequences of expressing the GnRH and SH genes within the same cells. By studying the structure and function of the GnRH:SH gene locus in this way, we hope to answer questions regarding the regulation of the reproductive control molecule GnRH, the function of the SH gene, and the significance of this novel eukaryotic genetic arrangement.
