Transcriptional regulation of iodothyronine deiodinases during embryonic development.
A single dose of chicken growth hormone (cGH) or dexamethasone acutely increases circulating T(3) levels in 18-day-old chicken embryos through a reduction of hepatic type III iodothyronine deiodinase (D3). The data in the present study suggest that this decrease in D3 is induced by a direct downregulation of hepatic D3 gene transcription. The lack of effect of cGH or dexamethasone on brain and kidney D3 activity, furthermore suggests that both hormones affect peripheral thyroid hormone metabolism in a tissue specific manner. Dexamethasone administration also results in an increase in brain type II iodothyronine deiodinase (D2) activity and mRNA levels that is also regulated at a transcriptional level. In contrast, however, cGH has no effect on brain D2 activity, thereby suggesting that either GH cannot pass through the blood-brain barrier in chicken or that cGH and dexamethasone regulate thyroid hormone deiodination by different mechanisms. In addition, the very short half-life of D2 and D3 (t(1/2)<1 h) in comparison with the longer half life of type I iodothyronine deiodinase (D1, t(1/2)>8 h), allows for D2 and D3 to play a more prominent role in the acute regulation of peripheral thyroid hormone metabolism than D1.
Van der Geyten
S
S
Laboratory of Comparative Endocrinology, Zoological Institute, K.U. Leuven, Naamsestraat 61, B-3000 Leuven, Belgium. serge.vandergeyten@bio.kuleuven.ac.be
Segers
I
I
Gereben
B
B
Bartha
T
T
Rudas
P
P
Larsen
P R
PR
Kühn
E R
ER
Darras
V M
VM
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000201:enzymology / Q000502:physiology; D002642:Chick Embryo; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005938:Glucocorticoids / Q000494:pharmacology; D013006:Growth Hormone / Q000494:pharmacology; D007453:Iodide Peroxidase / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000196:embryology / Q000201:enzymology / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000196:embryology / Q000201:enzymology / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013974:Thyroxine / Q000097:blood; D014158:Transcription, Genetic; D014284:Triiodothyronine / Q000097:blood; D000097564:Iodothyronine Deiodinase Type II
D003513:Cycloheximide; D003609:Dactinomycin; D003907:Dexamethasone; D005938:Glucocorticoids; D013006:Growth Hormone; D007453:Iodide Peroxidase; D011500:Protein Synthesis Inhibitors; D013974:Thyroxine; D014284:Triiodothyronine; D000097564:Iodothyronine Deiodinase Type II; C117274:iodothyronine deiodinase type III