Regulation of uncoupling protein messenger ribonucleic acid and 5'-deiodinase activity by thyroid hormones in fetal brown adipose tissue

We studied the regulation of type II 5'-deiodinase (5'D-II) activity and uncoupling protein (UCP) messenger RNA (mRNA) by thyroid hormones in fetal brown adipose tissue (BAT). Fetuses were obtained from hypothyroid pregnant rats infused with increasing doses of T-4 or T-3. Infusion of T-4 into hypothyroid pregnant rats increased T-4 and T-3 concentrations and inhibited 5'D-II activity in fetal BAT. In contrast, infusion of T-3 increased BAT 5'D-II activities at low, normal, or high BAT T-3 concentrations. The relationship between thyroid hormone concentrations in fetal BAT and plasma showed that BAT T-3 concentrations are relatively stable, increasing less than 2-fold over a wide range of circulating T-4 (3-fold) or T-3 (8-fold) concentrations. Most T-3 in fetal BAT are locally derived from T-4 and not from plasma T-3. UCP mRNA expression decreased to 30% of control values in hypothyroid fetuses. UCP mRNA levels were restored to normal in parallel with BAT T-3 concentrations after the infusion of either T-4 or T-3. UCP mRNA levels correlate well with BAT T-3 concentrations. Supraphysiological doses of T-4 did not further increase either BAT T-3 or UCP mRNA levels. T-3 might regulate basal UCP mRNA expression during fetal life.