The effects of thyroid hormones on fetal metabolism during late gestation were examined by measuring the rates of glucose and oxygen utilization rates in chronically catheterized sheep fetuses made hypothyroid by either fetal thyroidectomy (TX) or hypophysectomy (HX). The values were compared with those in intact fetuses and in thyroxine (T4)-treated TX and HX fetuses. 2. Umbilical O2 uptake expressed on a weight-specific basis was reduced by 20-30% in the hypothyroid fetuses and was restored to normal values when plasma T4 levels were maintained in the TX and HX fetuses by exogenous T4 administration. 3. The low O2 consumption rates of the untreated hypothyroid fetuses were accompanied by fetal growth retardation, an abnormal blood gas status, and in the TX fetuses, by significant reductions in the rates of glucose oxidation, CO2 production from glucose carbon and O2 utilization for glucose oxidation. 4. When T4 levels were maintained in the TX fetuses, these metabolic rates and fetal blood gas status were restored to their normal values. Replacement of T4 also sustained growth in TX but not in HX fetuses. 5. When the data from all fetuses were combined irrespective of treatment, there were significant positive correlations between plasma levels of T4 (but not triiodothyronine (T3)) and the rates of umbilical O2 uptake, glucose oxidation, CO2 production from glucose carbon and O2 utilization for glucose oxidation in the individual fetuses. 6. These findings demonstrate that T4 is a physiological regulator of O2 utilization by the sheep fetus close to term.
