CHARACTERIZATION OF GONADAL RECEPTORS AND GONADOTROPIN BIOLOGICAL ACTIVITY

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This project is concerned with studies on the molecular structure and function of gonadotropin receptors. We previously elucidated the genomic structure of the luteinizing hormone (LH) receptor and identified 10 introns within the gene sequence that encodes the extracellular domain of the receptor molecule. With the isolation of a splicing variant of the rat testicular LH receptor that is expressed as a secretion product from transfected COS cells, we have demonstrated that the extracellular domain of the LH receptor, which encompasses the region spanning exons 1-10, possesses the required structure for high- affinity binding of gonadotropin. Recent studies have concentrated on the characterization of the promoter and regulatory regions of the LH receptor gene, and transbinding factors involved in basal transcription. A Tata-less promoter domain was localized within the 173 bp 5~ flanking region of the gene. Within this region, cis elements/transbinding factors responsible for stimulatory/inhibitory control of the gene and tissue-specific expression were identified. In addition, we have defined regions located upstream of the promoter domain that repress transcription and may account for the lack of receptor expression in non-expressing cells, and have identified the element involved in this repression as well as DNA transbinding protein(s) that interact with this element and sequences of the promoter domain. Our studies indicate that a mechanism of depression accompanies transcriptional initiation in the LH receptor gene and that gene expression may result from mechanisms that alter specific trans/trans interactions between upstream elements and the two promoter domains.