Ethanol Has Direct Inhibitory Effects on Steroidogenesis in Human Granulosa Cells: Specific Inhibition of LH Action

Abstract

We have evaluated the direct effects of ethanol (EtOH) on the production of progesterone (P) and estradiol-17 beta (E2) by cultured human granulosa cells obtained during in vitro fertilization procedures. On day 3 of culture, cells were divided into control and ethanol (20 mM) groups and stimulated by hFSH (50 ng/ml), hLH (0-50 ng/ml), FSH+LH, 8 Br-cAMP (0.25 mM) and androstenedione (10(-7) M). Experiments were terminated on days 7 and 9 and DNA, P, and E2 were measured. Ethanol inhibited P and E2 secretion stimulated by LH; however, there was no significant effect of ethanol on P and E2 production in the control group or when the cells were stimulated by FSH or cAMP. EtOH also had no effect on androstenedione stimulated E2 production. There was no significant difference in the DNA contents of the human granulosa cells in the ethanol group as compared with the control group. These results are the first demonstration of a direct effect of ethanol on cultured granulosa-lutein cells and suggest that ethanol may inhibit action of LH on the corpus luteum. A direct selective toxic effect of EtOH on the ovary may be responsible for some of the reproductive abnormalities observed in alcoholic women.