The effect of follicle-stimulating hormone-suppressing protein or follistatin on luteinizing bovine granulosa cells in vitro and its antagonistic effect on the action of activin.

The time- and dose-dependent effects of bovine FSH-suppressing protein (FSP)/follistatin and human recombinant activin A (hr-Act) on oxytocin (OT) and progesterone (P) production, markers of luteinization, were studied in mature and immature bovine granulosa cells (GC), using three forms of FSP (31, 35, and 39 kDa) and a FSP pool consisting of 35, 39, and 45 kDa forms. FSP alone had no detectable effect on OT and P production when added to cultures of fully differentiated bovine GC. On the other hand, all FSP forms (10-100 ng/ml) enhanced and prolonged OT and P production of immature GC induced by bovine LH (10 ng/ml). Overall, 35 kDa FSP was more effective than the other forms tested. Hr-Act alone had a dose-dependent inhibitory effect on OT and P production on LH-stimulated immature GC. All four forms of FSP (30 or 100 ng/ml) added to cultures treated with hr-Act, reversed the inhibitory effect of hr-Act, with a significant increase (25%) above control levels using the 35 and 39 kDa FSP forms. In conclusion, FSP enhanced and prolonged the luteinization process, as indicated by OT and P production induced in immature GC by bovine LH, and was able to antagonize the inhibitory effect of hr-Act in this system. These studies suggest a physiological role for activin and FSP, as modulators of folliculogenesis and luteinization in the ovary. We propose that activin and FSP act in an autocrine fashion on GC in the ovarian follicle to regulate folliculogenesis and luteinization.