Inhibitory effect of gossypol on basal and luteinization factor-stimulatedprogesterone synthesis in porcine granulosa cells

Gossypol, a polyphenolic aldehyde, inhibits steroidogenesis and the reprodu ctive system in both sexes. The present study was undertaken to investigate whether gossypol may affect progesterone biosynthesis in cultured porcine granulosa cells isolated from small (1-2 mm) follicles (SGC). SGC were cult ured with gossypol, NO donor S-nitroso-N-acetylpenicillamine (S-NAP) or the specific NO-synthase inhibitor N-nitro-L-arginine methyl eater (L-NAME), i n the presence or absence of follicular fluid isolated from large (5-8 mm) follicles (LFF) or conditioned media (CM) of granulosa cells isolated from large follicles (LGC). Gossypol enhanced the nitrite content in culture med ia of SGC and inhibited basal progesterone secretion by SGC, S-NAP (10(-3)M ) inhibited progesterone secretion and enhanced the formation of cGMP by SG C. L-NAME had no effect on progesterone accumulation by SGC. The stimulator y effect of LFF or CM media on progesterone production by SGC in culture wa s also inhibited by S-NAP (10(-3)) and gossypol (10(-4)M). Moreover, gossyp ol inhibited forskolin-stimulated progesterone secretion, as well as substr ate-enhanced conversion of 22-OH-cholesterol and pregnenolone to progestero ne. These results suggest that the inhibitory effect of gossypol on progest erone secretion in culture of SGC may be mediated via NO generation.