Basic fibroblast growth factor as a regulator of ovarian granulosa cell differentiation: a novel non-mitogenic role

The role of basic fibroblast growth factor (bFGF) in ovarian granulosa cell differentiation was investigated in vitro. To this end, use was made of a primary culture of rat granulosa cells the differentiation of which was monitored by the acquisition of aromatase activity. Concurrent treatment with highly purified bFGF (10 ng/ml) produced a significant (P less than 0.05), albeit reversible inhibition (88 +/- 6%) of FSH (but not basal)-supported aromatization. Although independent of the FSH dose employed and of cell density, bFGF-attenuated aromatase activity proved dose-dependent, with a projected minimal effective dose of 0.11 +/- 0.03 ng/ml (7.5 +/- 2 pM), and an apparent median inhibitory dose of 0.63 +/- 0.09 ng/ml (43 +/- 6 pM). Unaccounted for by alterations in granulosa cell number, plating efficiency, or viability, the ability of bFGF to attenuate FSH hormonal action proved partly attributable to site(s) of action distal, rather than proximal to cAMP generation. Taken together, these observations indicate that the cytodifferentiative and replicative actions of bFGF in the granulosa cell can be dissociated, and lend additional support to the prospect that bFGF, possibly of intraovarian origin, may play a role in granulosa cell differentiation in the course of their ontogeny.