MATERNAL ADRENALECTOMY ELIMINATES A SURGE OF PLASMA DEHYDROEPIANDROSTERONE IN THE MOTHER AND ATTENUATES THE PRENATAL TESTOSTERONE SURGE IN THE MALE FETUS

Previous work has established a number of sex-related deficits in immu ne function, behavior, and endocrine responses to stress in the offspr ing of dams exposed to ethanol. To examine the potential role of mater nal glucocorticoids as a mediator of these sexually dimorphic effects in the fetus, we examined the influence of prenatal alcohol exposure i n the presence or absence of maternal glucocorticoids on fetal plasma corticosterone (CORT) production. An additional question to be address ed by these studies was whether maternal adrenalectomy could eliminate the known inhibition by ethanol of the prenatal surge of plasma testo sterone in male fetuses. Pregnant dams were adrenalectomized (ADX) or sham-adrenalectomized on gestational day (G) 7 and placed on a liquid diet containing 35% ethanol-derived calories or pair-fed an isocaloric control diet throughout the experiment. On G18, G19, and G21, plasma levels of CORT, testosterone, and dehydroepiandrosterone (DHEA) were m easured in male and female fetuses and their mothers. Ethanol administ ration consistently increased maternal plasma CORT levels but did not significantly alter CORT levels in the fetus. Maternal ADX resulted in compensatory increases in fetal CORT levels that were lower in fetuse s of ADX dams on alcohol, suggesting a direct effect of ethanol on fet al pituitary-adrenal activity. There were no significant sex differenc es in fetal plasma CORT levels in response to ang of these manipulatio ns. A novel surge of maternal plasma DHEA was found on G19 that was ab sent in plasma from ADX dams. In spite of the absence of a surge on G1 9, plasma DHEA levels of ADX dams rose from very low levels at G18 to levels on G21 that were significantly higher than in Sham dams. A norm al testosterone surge was observed in male fetuses on G18 and G19 from sham-adrenalectomized dams administered the pair-fed diet. However, t his surge was greatly attenuated in males administered ethanol and als o in male fetuses from ADX dams. These results reveal a direct inhibit ory influence of ethanol on fetal CORT secretion as well as on the pre natal testosterone surge in males. Furthermore, these studies demonstr ate the presence of a surge of DHEA in the pregnant rat. Overall, thes e data suggest that there is a critical adrenal factor in the rat that regulates the maternal surge of DHEA on G19 and the prenatal testoste rone surge of male fetuses on G18-19.