Developmental control of iodothyronine deiodinases by cortisol in the ovine fetus and placenta near term.
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.
Forhead
Alison J
AJ
Department of Physiology, Development, and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, United Kingdom. ajf1005@cam.ac.uk
Curtis
Katrina
K
Kaptein
Ellen
E
Visser
Theo J
TJ
Fowden
Abigail L
AL
D000818:Animals; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005333:Fetus / Q000201:enzymology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005865:Gestational Age; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology*; D007453:Iodide Peroxidase / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal; D012756:Sheep; D014284:Triiodothyronine / Q000097:blood; D000097564:Iodothyronine Deiodinase Type II
D006854:Hydrocortisone; D007453:Iodide Peroxidase; D014284:Triiodothyronine; D000097564:Iodothyronine Deiodinase Type II; C109812:iodothyronine deiodinase type I; C117274:iodothyronine deiodinase type III