High- and low-density lipoproteins stimulate progesterone production in cultured human granulosa cells

Cultured human granulosa cells are dependent upon gonadotrophins and exogenous cholesterol for maximal progesterone production. In previous studies low-density lipoproteins (LDLs) have been considered the preferred source of cholesterol, while high-density lipoproteins (HDLs) seemed rather to reduce progesterone synthesis in these cells. In this study, granulosa cells were harvested from 12 women and cultured in medium containing lipoprotein-deficient serum for 3 days. This was followed by 2 days of culture in medium supplied with LDL or HDL fractions, prepared by sequential ultracentrifugation and affinity chromatography. In the presence of LH, both lipoprotein fractions enhanced progesterone secretion in a concentration-dependent fashion while basal progesterone secretion was enhanced to a lesser extent. Progesterone secretion in response to lipoproteins did not differ between cells from pre-ovulatory follicles stimulated with gonadotrophins in vivo and less mature follicles obtained earlier in the menstrual cycle. We conclude that human granulosa cells in vitro can utilize cholesterol carried by HDL as well as LDL for progesterone synthesis.