FSH increases the synthesis and stores of cholesterol in porcine granulosa cells

Abstract

The effect of follicle-stimulating hormone (FSH) on cholesterol biosynthesis was studied using a recently developed serum-free medium for the culture of porcine granulosa cells. Both cell proliferation and progesterone production were shown to be dependent on de novo cholesterol synthesis in studies with an inhibitor of HMG-CoA reductase. Under basal conditions, mevalonate levels appeared to be rate-limiting for steroidogenesis but not for cell growth. FSH treatment increased [1-14C]acetate incorporation into sterols and the intracellular content of free and esterified cholesterol. These effect were not abolished when steroidogenesis was inhibited at the cholesterol side-chain cleavage step. Estradiol also stimulated [1-14C]acetate incorporation into sterols. Quantification of progesterone secretion after blockade of cholesterol synthesis revealed the presence of intracellular pools of precursor sterols which required depletion before progesterone secretion ceased. These pools, which were tentatively ascribed to cholesterol and pregnenolone, were increased in FSH-treated cells. Stimulation of cholesterol biosynthesis may play a fundamental role in FSH action on these cells.