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Developmental Control of Iodothyronine Deiodinases by Cortisol in the Ovine Fetus and Placenta Near Term

Department of Physiology, Development, and Neuroscience (A.J.F., K.C., A.L.F.), University of Cambridge, Cambridge CB2 3EG, United Kingdom; and Department of Internal Medicine (E.K., T.J.V.), Erasmus Medical Center, 3015 GE Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: Dr. A. J. Forhead, Department of Physiology, Development, and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, United Kingdom. E-mail: ajf1005{at}cam.ac.uk.

Preterm infants have low serum T₄ and T₃ 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 T₃ and produces rT₃ from T₄. In human and ovine fetuses, plasma T₃ rises near term in association with the prepartum cortisol surge. This study investigated the developmental effects of cortisol and T₃ on tissue deiodinases and plasma thyroid hormones in fetal sheep during late gestation. Plasma cortisol and T₃ 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 T₃, and D1 (hepatic, renal, perirenal adipose tissue) and D3 (cerebral), and decrements in renal and placental D3 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 T₃ alone increased hepatic D1 and decreased renal D3 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 T₃, may be responsible for the rise in plasma T₃ concentration near term. Some of the maturational effects of cortisol on deiodinase activity may be mediated by T₃.

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