Prenatal programming of adult thyroid function by alcohol and thyroid hormones

Abstract

Increasing evidence associates environmental challenges early in life with permanent alterations of physiological functions in adulthood. These changes in fetal environment can trigger physiological adaptations by the fetus, called fetal programming, which may be beneficial before birth but permanently influence the physiology of the organism. In this study, we investigated the potential connection between alcohol-induced decreased maternal thyroid function and the hypothalamic-pituitary-thyroid (HPT) function of adult rat offspring. Plasma 3,5,3′-triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) levels were decreased in alcohol-consuming (E) dams on gestational day 21 compared with ad libitum- (C) and pair-fed (PF) controls. No significant differences were found in HPT function in young offspring (3 wk of age) between diet groups. However, adult fetal alcohol-exposed (FAE) offspring had significantly decreased levels of T3 along with elevated TSH compared with control offspring. T4 administration to the mother did not normalize the hypothyroid state of the adult FAE offspring. Interestingly, administration of T4 to control pregnant dams decreased plasma T3 of the adult female offspring only, whereas T4 together with maternal alcohol consumption or pair-feeding led to decreased TSH and T4 in the adult female offspring. Our results suggest that ethanol consumption and T4 administration alter maternal HPT function, leading to prenatally programmed permanent alterations in the thyroid function of the adult offspring.