Abstract
Alcohol-mediated alterations in hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid axis function are two proposed mechanisms by which alcohol causes neurodevelopmental injury to the fetus. We previously reported that third-trimester equivalent only alcohol exposure in sheep results in increases in the maternal and fetal adrenocorticotropin and cortisol levels, and decreases in the fetal thyroid hormones T(3) and T(4) and maternal T(3) levels. In this study, we wished to characterize the maternal HPA and hypothalamic-pituitary-thyroid hormone responses to repeated binge alcohol exposure during all three-trimester equivalents of pregnancy in sheep. Pregnant ewes received intravenous infusions of alcohol at doses of 0.75, 1.25, or 1.75 g/kg over 1h with mean peak blood alcohol concentrations of 90, 126, or 183 mg/dl, respectively, on 3 consecutive days each week beginning on gestational day (GD) 4. Maternal blood samples were collected on GDs 6, 40, 90, and 132. Maternal plasma concentrations of adrenocorticotropin and cortisol increased in response to the high alcohol dose, and the magnitude of these elevations was not different across gestation. Thyroid hormone levels were not different when comparing among treatment groups at any time point during gestation. However, there was an ontogenetic decrease in the maternal T(3) concentration beginning between GDs 6 and 40 and a decrease in maternal T(4) and free T(4) beginning between GDs 40 and 90. The current findings suggest that (1) maternal alcohol consumption at any time during gestation stimulates the HPA axis, (2) maternal HPA responsiveness to alcohol does not change across gestation, (3) binge alcohol exposure at these doses lasting all three-trimester equivalent of human brain development does not reduce maternal thyroid hormone concentration, (4) alterations in fetal thyroid function in response to alcohol exposure do not occur as a result of diminished maternal thyroid hormone contribution, and (5) there is an ontogenetic decrease in ovine maternal thyroid hormones over gestation.