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

The acquisition of FSH receptor(s) during follicular growth and their coupling to signaling pathways are key events in follicular development and dominance. However, little is known about the precise nature of the FSH receptor(s) involved in the growth-promoting phases of hormone action. To investigate the hormonal regulation of a newly discovered, alternatively spliced, growth factor type 1 receptor (designated FSH-R3) for the hormone, we examined expression in the adult mouse and the effect of PMSG treatment in the immature mouse ovary. Using RT-PCR and primers based on the established sheep ovarian transcript, a part of the FSH-R3 message was amplified only in wild-type (+/+), but not in the FSH-R knockout (-/-), mouse ovary. Semiquantitative RT-PCR using 3'-end primers specific for FSH-R1 (G(s)-coupled) and FSH-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 protein was detected by Western blotting in extracts of adult mouse ovary and was localized in granulosa cell membrane of mature follicles. In the immature mouse, levels of FSH-R3 protein that increased after PMSG administration in a time-dependent manner were also localized only on granulosa cell membranes of large follicles. The results reveal for the first time the expression of a different growth-promoting receptor for FSH in the developing and cycling mouse ovary. These observations introduce a new paradigm in the control of ovarian function.