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, diethylstilbestrol-primed rats were cultured for up to 72 h under serum-free conditions in the absence or presence of FSH (100 ng/ml). Media conditioned by untreated granulosa cells revealed constitutively released polyethylene glycol (PEG)-precipitable [125I] IGF-I binding activity the daily elaboration of which proved constant throughout the 72 h experimental period. However, treatment of granulosa cells, with FSH resulted in dramatic inhibition of the accumulation of IGF-I binding activity (89% at the 100 ng/ml dose level). Systemic provision of FSH (10 micrograms/rat/day for 2 days) revealed that this gonadotropic action is not strictly an in vitro phenomenon but that it can be fully 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 (28-29 kDa) as well as a single minor band (23 kDa). Treatment with FSH virtually eliminated the 23 kDa species and substantially reduced the relative representation of the 28 and 29 kDa IGF-BP species (82 and 74% inhibition, respectively). Taken together, these observations disclose the multiplicity of granulosa cell-derived IGF-BPs 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 FSH 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-1 to its cognate cell surface receptors and hence its cellular hormonal action.
Department of Obstetrics/Gynecology, University of Maryland School of Medicine, Baltimore 21201.
E Y
EY
Adashi
C E
CE
Resnick
E R
ER
Hernandez
A
A
Hurwitz
R G
RG
Rosenfeld
D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D004054:Diethylstilbestrol / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008970:Molecular Weight; D051381:Rats
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D004054:Diethylstilbestrol; D005640:Follicle Stimulating Hormone