STRUCTURAL ORGANIZATION OF THE FOLLICLE-STIMULATING-HORMONE RECEPTOR GENE

We have characterized a series of rat genomic clones that code for the FSH receptor (FSHR) gene and approximately 14.8 kilobases of DNA up-stream of the transcriptional start sites. Southern blot analysis indicated that there was only a single gene for the FSHR. Primer extension and S1 nuclease experiments revealed the presence of two major transcriptional start sites at positions -80 and -98 relative to the translational start site. Transient expression studies of a fusion gene containing 830 basepairs of DNA 5' to the translational start site linked to the reporter gene chloramphenicol acyltransferase have shown that this portion of the gene is capable of acting as a transcriptional promoter in rat Sertoli cells. The FSHR gene contained 10 exons and nine introns. The first nine exons encoded the extensive amino-terminal domain of the receptor, while the last exon encoded the transmembrane-spanning and cytoplasmic domains. A repeated motif similar to that observed in the leucine-rich glycoprotein family was delineated within exons 2-9. Comparison of the FSHR gene to the LH receptor gene revealed a number of striking similarities which clearly indicate that these receptors evolved through gene duplication. The ancestral gene for these receptors presumably arose from a series of tandem duplications of the leucine-rich motif, which when combined with the common ancestral gene of the G-protein-coupled receptor family led to the current gene structure of the glycoprotein hormone receptors.