Maternal adrenocorticotropin, cortisol and thyroid hormone responses to chronic binge alcohol exposure throughout gestation: ovine model

This study investigated the effect of chronic alcohol exposure on the responses of the maternal hypothalamus-pituitary adrenal axis (HPA-axis) and thyroid hormones throughout gestation using an ovine model. Maternal plasma concentrations of ACTH, cortisol and the thyroid hormones T3, free T4 and total T4 were determined in response to infusion of 0.75, 1.25 and 1.75 g/kg alcohol. Maternal endocrine responses to alcohol administration have been investigated before in rodent models. However, this is the first study using a large animal model (sheep), in which all three human trimester equivalents occur in utero. Different concentrations of alcohol were administered intermittently from gestational day 4 to 132 in a pattern that modeled human binge drinking during pregnancy. Maternal blood samples were collected on specific days (GD 6, 40, 90, 132) and at multiple time-points (0, 0.5, 1, 1.5, 2, 6, 24 hours) and were analyzed to determine blood alcohol concentrations (BACs) and ACTH, cortisol, free T4, total T4 and T3 plasma concentrations. Alcohol readily permeates the placenta and can directly affect fetal cells and tissues. Alcohol also causes endocrine imbalances in the mother and interferes with maternal-fetal hormonal interactions and the mother?s ability to maintain a healthy pregnancy, thus also indirectly affecting fetal development. Sheep receiving either 0.75, 1.25 or 1.75 g/kg alcohol achieved peak BAC values of 93 + 5, 126 + 5 and 183 + 5 respectively. Alcohol exposure resulted in increased plasma ACTH and cortisol concentrations peaking at 2 hours after beginning of the infusion and returning to baseline values at 6 hours after beginning of the infusion. There was no effect of alcohol on any of the plasma thyroid hormone concentrations. Thyroid hormone concentrations changed as a result of progressing pregnancy. Plasma concentrations of total T4 and free T4 were higher on gestational days 6 and 40 compared to GDs 90 and 132, and plasma T3 concentrations were highest on GD 6. The results of this study show that alcohol stimulates the HPA-axis in a dose dependent fashion in pregnant sheep. The response of the HPA-axis to repeated alcohol exposure throughout gestation remained unchanged. Alcohol exposure did not affect the release of thyroid hormones. Thyroid hormone concentrations changed during pregnancy in sheep in a manner similar to changes observed in pregnant women.