Differential effects of maternal dexamethasone treatment on circulating thyroid hormone concentrations and tissue deiodinase activity in the pregnant ewe and fetus.
Clinically, treatment of pregnant women at risk of preterm delivery with synthetic glucocorticoids accelerates fetal maturation. This study investigated the effect of maternal dexamethasone treatment, in clinically relevant doses, on plasma thyroid hormone concentrations and tissue deiodinase activities (D1, D2, and D3) in ewes and their fetuses. From 125 d of gestation (term 145 +/- 2 d), pregnant ewes were injected twice im with either saline (2 ml of 0.9% NaCl, n = 11) or dexamethasone (2 x 12 mg in 2 ml of saline, n = 10) at 24-h intervals. Maternal dexamethasone treatment increased plasma T(3) and reverse T(3) (rT(3)), but not T(4), concentrations in the fetuses. In the dexamethasone-exposed fetuses, hepatic D1 activity was higher, and renal and placental D3 activities were lower, than in the saline-exposed fetuses. In the ewes, plasma concentrations of T(3) and T(4) were reduced, and rT(3) increased, by dexamethasone treatment without any change in tissue deiodinase activity. Therefore, maternal dexamethasone treatment has different effects on the thyroid hormone axis of the pregnant ewe and fetus. In the fetus, the dexamethasone-induced rise in circulating T(3) may be due to both increased hepatic production of T(3) from T(4), and reduced clearance of T(3) by the kidney and placenta. Changes in T(3) bioavailability may mediate some of the maturational effects of antenatal glucocorticoid treatment in the preterm fetus.
Forhead
Alison J
AJ
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, United Kingdom. ajf1005@cam.ac.uk
Jellyman
Juanita K
JK
Gardner
David S
DS
Giussani
Dino A
DA
Kaptein
Ellen
E
Visser
Theo J
TJ
Fowden
Abigail L
AL
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005312:Fetal Blood; D005333:Fetus / Q000201:enzymology*; D005938:Glucocorticoids / Q000494:pharmacology*; D007453:Iodide Peroxidase / Q000378:metabolism*; D007668:Kidney / Q000196:embryology; D008099:Liver / Q000196:embryology; D009994:Osmolar Concentration; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D012756:Sheep; D013963:Thyroid Hormones / Q000097:blood*; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D005938:Glucocorticoids; D013963:Thyroid Hormones; D014284:Triiodothyronine; D003907:Dexamethasone; D007453:Iodide Peroxidase; D013974:Thyroxine