Time-dependent effects of follicle-stimulating hormone on progesterone metabolism by cultured rat granulosa cells.

The effects of FSH on the accumulation of endogenous progesterone and 20 alpha-hydroxy-4-pregnen-3-one as well as on the metabolism of [4-14C]progesterone were studied in 24, 48 and 72 h cultures of rat granulosa cells. FSH stimulated the accumulation of both progesterone and 20 alpha-hydroxy-4-pregnen-3-one by 6-18 fold and 2.5-44 fold, respectively. Short term exposure (24 h) to FSH resulted in the ratio of progesterone to 20 alpha-hydroxy-4-pregnen-3-one accumulations significantly increased (by 2.6 fold), while the reverse was observed for the longer (48 and 72 h) cultures whereby control levels of the ratio of progesterone to 20-alpha-hydroxy-4-pregnen-3-one were significantly greater (by 50% and 270%, respectively) than those of FSH-treated cultures. Effects of FSH on [4-14C]progesterone were also time-dependent. Twenty-four hour cultures were associated with FSH induced inhibition of 20 alpha-reduced metabolites of progesterone (by 55%) while the 48 and 72 h exposures to FSH resulted in a significant increase of the 20 alpha-reduced metabolites above control levels (by 73% and 230%, respectively). Consequently, it is postulated that FSH may exert biphasic time-dependent actions on 20 alpha-hydroxysteroid dehydrogenase activity with short term inhibitory and longer term stimulatory effects.