FOLLICLE-STIMULATING-HORMONE INHIBITS THE CONSTITUTIVE RELEASE OF INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS BY CULTURED RAT OVARIAN GRANULOSA-CELLS

The ovarian granulosa cell has previously been shown to be a site of insulin-like growth factor (IGF)-I production, reception, and action. It is the purpose of this communication to explore the possibility that this cell type is also capable of hormonally-regulatable elaboration of IGF binding proteins (BPs). To this end, granulosa cells from immature, diethylstiIbestrol-primed rats were cultured for up to 72h under serum-free conditions in the absence or presence of FSH (l00ng/ml). Media conditioned by untreated granulosa cells revealed constitutively released polyethylene glycol (PEG)-precipitabie [125I] IGF-I binding activity the daily elaboration of which proved constant throughout the 72h experimental period. However, treatment of granulosa cells with FSH resulted in dramatic inhibition of the accumulation of IGF-I binding activity (89% at the l00ng/ml dose level). Systemic provision of FSH (10µg/rat/day for 2 days) revealed that this gonadotropic action is not strictly an in vitro phenomenon but that i t can be f u l l y reproduced under in vivo circumstances. Western ligand blotting of SDS-PAGE-fractionated media conditioned by untreated granulosa cells revealed three IGF-BP species comprising a major band doublet (28-29kDa) as well as a single minor band (23kDa). Treatment with FSH virtually eliminated the 23kDa species and substantially reduced the relative representation of the 28 and 29kDa IGF-BP species (82 and /4% inhibition, respectively). Taken together, these observations disclose the multiplicity of granulosa cell-derived IGFBPs and reveal the striking ability of FSH to suppress their constitutive release under both in vitro and in vivo circumstances. This FSH action is all the more noteworthy in light of the generally stimulatory effect exerted by FSH at the level of the granulosa cell. Inasmuch as l-SH may be concerned with the promotion of granulosa cell development, its ability to attenuate the release of (presumptively inhibitory) IGF-BPs may enhance the access of endogenously-produced IGF-I to its cognate cell surface receptors and hence its cellular hormonal action. © 1990 by The Endocrine Society.