Developmental control of iodothyronine deiodinases by cortisol in the ovine fetus and placenta near term

Preterm infants have low serum T-4 and T-3 levels, which may partly explain the immaturity of their tissues. Deiodinase enzymes are important in determining the bioavailability of thyroid hormones: deiodinases D1 and D2 convert T4 to T3, whereas deiodinase D3 inactivates T-3 and produces rT(3) from T-4. In human and ovine fetuses, plasma T-3 rises near term in association with the prepartum cortisol surge. This study investigated the developmental effects of cortisol and T-3 on tissue deiodinases and plasma thyroid hormones in fetal sheep during late gestation. Plasma cortisol and T-3 concentrations in utero were manipulated by exogenous hormone infusion and fetal adrenalectomy. Between 130 and 144 d of gestation (term 145 +/- 2 d), maturational increments in plasma cortisol and T-3, and D1 (hepatic, renal, perirenal adipose tissue) and D3 (cerebral), and decrements in renal and placental D-3 activities were abolished by fetal adrenalectomy. Between 125 and 130 d, iv cortisol infusion raised hepatic, renal, and perirenal adipose tissue D1 and reduced renal and placental D3 activities. Infusion with T-3 alone increased hepatic D1 and decreased renal D-3 activities. Therefore, in the sheep fetus, the prepartum cortisol surge induces tissue- specific changes in deiodinase activity that, by promoting production and suppressing clearance of T-3, may be responsible for the rise in plasma T-3 concentration near term. Some of the maturational effects of cortisol on deiodinase activity may be mediated by T-3.