Developmentally defined regulation of thyroid hormone metabolism by glucocorticoids in the rat.
Glucocorticoids are known regulators of thyroid function in vertebrates. In birds they have clear tissue-specific and age-dependent effects on thyroid hormone metabolism. In mammals, however, few studies exist addressing these aspects using an in vivo model system. We therefore set out to examine the acute effects of a single dose of dexamethasone (DEX) on plasma 3,5,3'-tri-iodothyronine (T(3)) and thyroxine (T(4)) levels, as well as on the activity of the different deiodinases in liver, kidney and brain in the developing rat. In 20-day-old fetuses (E20), glucocorticoids had no effects on circulating thyroid hormone levels despite their clear effects on hepatic and renal deiodinases, thereby indicating that under these conditions circulating thyroid hormone levels are more dependent on thyroidal secretion than on peripheral deiodination. In contrast, in 5-day-old rat pups, DEX did not seem to have any effects on hepatic and renal T(3) production (via the type I deiodinase), whereas type III deiodinase (D3) activity in both these tissues increased significantly. These observations therefore suggested that the DEX-induced increase in circulating T(3) levels is a direct consequence of the increase in plasma T(4) levels. In 12-day-old pups (P12), however, the main effect of glucocorticoids on circulating levels was by increasing inner ring deiodination T(3) through induction of D3 in both liver and kidney. Finally, in the brain, glucocorticoids stimulated thyroid hormone activity only during a short period of time (between E20 and P12) that largely overlaps with the transient window in time during which brain development is thyroid hormone sensitive. This was in contrast to the E20 and P12 brain, where the glucocorticoid-induced changes in type II deiodinase and D3 seemed to favor a status quo in local T(3) availability.
Van der Geyten
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Laboratory of Comparative Endocrinology, Zoological Institute, KU Leuven, Naamsestraat 61, B-3000 Leuven, Belgium. serge.vandergeyten@bio.kuleuven.ac.be
Darras
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D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000196:embryology / Q000201:enzymology; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology*; D007453:Iodide Peroxidase / Q000378:metabolism; D007668:Kidney / Q000196:embryology / Q000201:enzymology; D008099:Liver / Q000196:embryology / Q000201:enzymology; D008297:Male; D011247:Pregnancy; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; 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