Follistatin inhibits activin-induced differentiation of rat follicular granulosa cells in vitro.
The effect of follistatin on activin-induced granulosa cell differentiation was investigated in freshly harvested granulosa cells from diethylstilbestrol (DES)-treated rats. Activin induced a remarkable change in granulosa cellular morphology from elongated fibroblast-like to round cells, which follistatin prevented. Follistatin itself had no influence on the cellular morphology. We studied the action of follistatin on activin-induced differentiation of granulosa cells cultured in a chemically defined medium. Addition of activin (30 ng/ml) to the culture increased the FSH binding site approximately 2-fold compared with the control (spontaneous expression) level, whereas follistatin reduced the activin-induced expression level to the control level in a concentration-dependent manner. Activin (30 ng/ml) markedly augmented FSH-induced hCG binding and progesterone production by approximately 20-fold, and these effects were suppressed by follistatin in a concentration-dependent manner. Similarly, addition of follistatin to the culture induced a concentration-dependent decrease of activin-enhanced inhibin-producing activity, but had no effect on FSH-induced inhibin production. These results suggest that follistatin/activin-binding protein binds to activin stoichiometrically to suppress the activin-induced differentiation of rat granulosa cell in vitro, but follistatin itself has no direct effect on activin-independent reactions.
Nakamura
T
T
Frontier Research Program, Institute of Physical and Chemical Research (RIKEN), Wako, Japan.
Hasegawa
Y
Y
Sugino
K
K
Kogawa
K
K
Titani
K
K
Sugino
H
H
D028341:Activins; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism; D004054:Diethylstilbestrol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D038681:Follistatin; D006023:Glycoproteins / Q000494:pharmacology*; D006107:Granulosa Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D007265:Inhibins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011962:Receptors, FSH / Q000378:metabolism; D011974:Receptors, LH / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology
D006063:Chorionic Gonadotropin; D038681:Follistatin; D006023:Glycoproteins; D011962:Receptors, FSH; D011974:Receptors, LH; D011994:Recombinant Proteins; D028341:Activins; D011374:Progesterone; D007265:Inhibins; D004054:Diethylstilbestrol; D005640:Follicle Stimulating Hormone