Identification of two novel, alternatively spliced mRNA transcripts of the human follicle-stimulating hormone receptor.

Glycoprotein hormone receptors contain large extracellular domains encoded by multiple exons that can be alternatively spliced. Using human ovarian surface epithelium, we cloned two new splice variants of the human follicle-stimulating hormone receptor (FSH-R) gene, hFSH-R2 and hFSH-R3. The hFSH-R2 splice variant differed from the full-length FSH-R mRNA by the deletion of exon 10 and inclusion of two small exons after exon 9 whereas the hFSH-R3 splice variant retained only exons 1-6 of the full-length transcript. Both variants were expressed at low levels, but were detected in cells from follicular fluid derived from 30 different subjects. Transfection of these two variants individually into KGN cells, an ovarian cancer cell line that expresses wild-type FSH-R, reduced FSH-mediated phosphorylation of ERK(1/2), Akt, and p38/MAPK. Furthermore, in vitro co-expression of either hFSH-R2 or hFSH-R3 and full-length FSH-R in HEK293T cells reduced signal transduction through full-length FSH-R. Further studies are needed to fully elucidate the functions of these receptor isoforms.