Alcohol inhibits epidermal growth factor-stimulated progesterone secretion from human granulosa cells

In this study, luteinized human granulosa cells (GC) obtained during in vitro fertilization procedures were used as a model system to evaluate the effects of ethanol (EtOH), a well-known reproductive toxin, on epidermal growth factor (EGF) and gonadotropin-stimulated steroidogenesis. Our results demonstrate that the basal progesterone (P-4) and estradiol (E(2)) secretion by human GC in vitro was dependent on the ovarian stimulation protocol. EGF significantly enhanced P-4, but not E(2), secretion in human GC from clomiphene citrate (CC), human menopausal gonadotropin (hMG), and hMG/gonadotropin-releasing hormone agonist (GnRH-a)-treated patients. The effects of EGF plus luteinizing hormone (LH) were additive in cells from the CC group, but less than additive in hMG and hMG/GnRH-a groups, EtOH at 20 mM or more inhibited EGF stimulated P-4 secretion in human GC from all three patient groups. EtOH inhibited P-4 secretion stimulated by EGF and LH cotreatment in the CC and hMG/ GnRH-a groups, but not in human GC from the hMG-treated patients. These results suggest that basal and EGF or LH-stimulated P-4 secretion by human GC, as well as the effects of EtOH, are profoundly influenced by the foliicle's hormonal milieu.