Hormone-induced receptor gene splicing: Enhanced expression of the growth factor type I follicle-stimulating hormone receptor motif in the developingmouse ovary as a new paradigm in growth regulation

The acquisition of FSH receptor(s) during follicular growth and their coupl ing to signaling pathways are key events in follicular development and domi nance. However, little is known about the precise nature of the FSH recepto r(s) involved in the growth-promoting phases of hormone action. To investig ate the hormonal regulation of a newly discovered, alternatively spliced, g rowth factor type 1 receptor (designated FSH-R3) for the hormone, we examin ed expression in the adult mouse and the effect of PMSG treatment in the im mature mouse ovary. Using RT-PCR and primers based on the established sheep ovarian transcript, a part of the FSH-RB message was amplified only in wil d-type (+/+), but not in the FSH-R knockout (-/-), mouse ovary. Semiquantit ative RT-PCR using 3'-end primers specific for FSH-R1 (G(s)-coupled) and FS H-R3 indicated expression levels of the latter to be higher when follicular growth was induced by PMSG. Using FSH-R3-specific peptide IgG, FSH-R3 prot ein was detected by Western blotting in extracts of adult mouse ovary and w as localized in granulosa cell membrane of mature follicles. In the immatur e mouse, levels of FSH-RS protein that increased after PMSC administration in a time-dependent manner were also localized only on granulosa cell membr anes of large follicles. The results reveal for the first time the expressi on of a different growth-promoting receptor for FSH in the developing and c ycling mouse ovary. These observations introduce a new paradigm in the cont rol of ovarian function.