Porcine follicular fluid protein(s) inhibit rat ovary granulosa cell steroidogenesis

Abstract

We examined the effect of an isolated fraction of follicular fluid, termed follicle regulatory protein, on the production of estrogen, progesterone, and 20α-dihydroprogesterone by cultured rat ovarian granulosa cells. We found a stepwise decrease in estrogen production with an increasing concentration of follicle regulatory protein (9 to 300 μg/ml) when the cells were stimulated by 6.25 ng/ml of ovine follicle-stimulating hormone, but the addition of a saturating dose of ovine follicle-stimulating hormone (50 ng/ml) prevented the inhibitory effect of follicle regulatory protein on estrogen production. Follicle regulatory protein inhibited progesterone production at both low and saturating levels of ovine follicle-stimulating hormone. We examined whether cholesterol substrate in the form of high-density lipoprotein or low-density lipoprotein could overcome the follicle regulatory protein inhibition of progesterone and 20α-dihydroprogesterone production stimulated by follicle-stimulating hormone. At all concentrations of high-density and low-density lipoprotein, 75 μg/ml of follicle regulatory protein inhibited progesterone production by 80% to 90%. In the case of 20α-dihydroprogesterone, the presence of high-density and low-density lipoprotein accentuated the inhibitory effect of follicle regulatory protein. These results demonstrate that the effects of follicle regulatory protein on ovarian steroidogenesis depend on: (1) the concentration of gonadotropin, (2) the concentration of follicle regulatory protein, and (3) the availability of cholesterol substrate.