Fuel utilization by early newborn brain is preserved under congenital hypothyroidism in the rat.

Abstract

Mental retardation associated with hypothyroidism may be caused by impairment of brain ketone body-metabolizing enzymes during the suckling period. However, much evidence suggests that, immediately after delivery, lactate, instead of ketone bodies or glucose, may be the best substrate for the brain. In this work, we have studied the effect of experimentally induced congenital hypothyroidism on the rate of lactate, glucose, and 3-hydroxybutyrate utilization in early neonatal brain slices. Methimazole (MMI) administration to the mothers caused a 5.4- and 1.7-fold decrease in neonatal plasma concentrations of L-thyroxine (T4) and 3,5,3'-triiodo-L-thyronine (T3), respectively. Propylthiouracil (PTU) administration to the mothers caused a 7.3- and > 2-fold decrease in plasma T4 and T3 concentrations, respectively. MMI-induced hypothyroidism did not significantly modify the rate of lactate, glucose, or 3-hydroxybutyrate oxidation to CO2 and their incorporation into lipids by the neonatal brain. However, PTU-induced hypothyroidism decreased the rate of lactate and glucose oxidation to CO2 and their incorporation into lipids by 17% (p < 0.05). 3-Hydroxybutyrate utilization was not modified by this treatment. Separation by HPLC of the lipids revealed that PTU-mediated inhibition of lipid synthesis from lactate and glucose may be accounted for by specific inhibition of the rate of sterol synthesis (15%, p < 0.05), whereas the rate of phospholipid synthesis was unaffected. These results suggest that the early newborn may develop mechanisms aimed at avoiding the possible brain damage caused by the inhibition of lipid synthesis brought about by mild neonatal hypothyroidism.