Chronic effects of prepubertal ethanol administration on steroidogenic acute regulatory protein in the rat ovary.
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BACKGROUND: A mitochondrial protein, steroidogenic acute regulatory protein (StAR), plays an essential role in steroidogenesis by facilitating delivery of cholesterol across the mitochondrial membrane. Because ethanol (EtOH) causes suppressed estradiol (E2) secretion in prepubertal female rats and rhesus monkeys, we evaluated the effects of chronic EtOH administration on prepubertal ovarian StAR. METHODS: Rats were implanted with a gastric cannula on day 24 and began receiving control or EtOH diets on day 28. At 0800 hr on day 33, the experimental groups were subdivided. Half of the EtOH-treated animals received a subcutaneous injection of pregnant mare serum gonadotropin (PMSG; 15 IU), and the other half received an injection of saline. The chow-fed and liquid-diet control groups were also subdivided, with half receiving the PMSG and the other half receiving saline. Eight hours after the respective injections, the animals were killed, and their ovaries and blood were collected. RESULTS: The ovaries from EtOH-treated rats showed decreased basal expression of both the 3.8-kb (p < 0.05) and 1.7-kb (p < 0.01) StAR transcripts. PMSG-stimulated animals not exposed to EtOH showed a more than 2-fold increase (p < 0.01) in the ovarian levels of both transcripts. Western blot analysis revealed that EtOH exposure decreased (p < 0.001) the basal expression of StAR protein, which paralleled the decrease in basal StAR messenger RNA. PMSG induced an increase (p < 0.001) in the levels of StAR protein, and this effect was blunted (p < 0.01) by EtOH. These changes observed in ovarian StAR protein were paralleled by decreases in serum pregnenolone and E2. CONCLUSIONS: These results demonstrate for the first time that ovarian StAR is a target for the chronic action of EtOH to alter prepubertal steroidogenesis, resulting in suppressed serum E2 secretion during a critical time of development.
