Regulation of thyroid hormone availability in liver and brain by glucocorticoids.
Glucocorticoids as well as thyroid hormones are essential for normal brain development. Exogenous glucocorticoids stimulate 3,3',5-triiodothyronine (T(3)) availability in circulation of birds and similar effects have been observed in sheep. Chicken data indicate that glucocorticoid administration also stimulates thyroid hormone metabolism in brain but the effects on local thyroid hormone concentrations are not known. Therefore, the current study: (1) determined local thyroid hormone availability in separate brain areas of 18-day-old embryonic chickens (E18) after injection of dexamethasone (DEX), and (2) investigated the impact on the thyroid hormone metabolic pathways in these brain parts and compared the results with the hepatic situation. For this, E18 chicken embryos were treated with a single intravenous dose of DEX (25 microg). Despite the decreased 3,5,3',5-tetraiodothyronine (T(4)) availability in the liver of the DEX treated embryos, the T(3) content was strongly increased, parallel to the plasma T(3) surge. This T(3) surge was primarily related to a fall in hepatic T(3) breakdown through a downregulation of the type III deiodinase (D3). The sulfation pathway in liver seems not to be affected by DEX. In all brain parts, DEX affects the T(3) production capacity by upregulation of the type II deiodinase (D2). This enables the brain to compensate for the decrease in T(4) availability, although the T(3) concentrations are not consistently increased like in plasma and liver. This observation points to the existence of a fine-tuning mechanism in brain that enables the brain to keep the T(3) concentrations within narrow limits.
Reyns
G E
GE
Laboratory of Comparative Endocrinology, Zoological Institute, K.U. Leuven, Naamsestraat 61, B-3000 Leuven, Belgium.
Verhoelst
C H J
CH
Kühn
E R
ER
Darras
V M
VM
Van der Geyten
S
S
D000818:Animals; D001921:Brain / Q000201:enzymology; D002642:Chick Embryo; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D013974:Thyroxine / Q000493:pharmacokinetics*; D014284:Triiodothyronine / Q000493:pharmacokinetics*
D005938:Glucocorticoids; D014284:Triiodothyronine; D003907:Dexamethasone; D013974:Thyroxine