Acute pretranslational regulation of type III iodothyronine deiodinase by growth hormone and dexamethasone in chicken embryos

Abstract

Both growth hormone (GH) and glucocorticoids are regulators of thyroid hormone metabolism in vertebrates. Studies on chicken embryos demonstrated that intravenous (iv) injection of chicken GH or glucocorticoids results in increased plasma 3,3′,5-triiodothyronine (T 3) concentrations, and this through a reduction of hepatic type III iodothyronine deiodinase (D3) activity. The recent cloning of chicken type I iodothyronine deiodinase (D1) and D3 offers the tools to investigate at what level (pre- or posttranslational) this downregulation of D3 occurs. Eighteen day old chicken embryos were injected with either 0.9% NaCl (control), 50 μg dexamethasone (DEX), or 20 μg cGH per animal. Plasma and tissue samples were taken 5, 10, 30, 60, 120, and 240 min post-injection. Plasma T 3 and thyroxine (T 4) were determined as well as in vitro hepatic D1 and D3 activities. Hepatic D1 and D3 mRNA levels were measured by both Northern analysis and competitive reverse transcription polymerase chain reaction (RT-PCR). Injection of GH or DEX resulted in a significant increase in plasma T 3 when compared to controls within 30 min post-injection. This increase remained until the end of the experiment in the DEX-treated group, but not in the GH group. GH administration had no influence on plasma T 4 levels, whereas DEX significantly reduced plasma T 4 from 30 min onwards. Hepatic D1 activity and D1 mRNA levels showed no changes. Hepatic D3 activity, however, decreased within 10 min after DEX administration and somewhat slower after GH administration (within 30 min). Hepatic D3 activity remained low for the remainder of the experiment in the DEX-treated group, whereas D3 activity gradually returned to control levels in the GH group. This change in hepatic D3 activity was paralleled by the changes in hepatic D3 mRNA levels ( r=0.88, P=0.0001) as confirmed by both Northern analysis and competitive RT-PCR. In conclusion, these results demonstrate that in embryonic chicken GH and DEX acutely increase plasma T 3 levels by decreasing hepatic D3 activity, a decrease that seems to be regulated predominantly at the pretranslational level. These results are also an indication for the short half life ( t 1/2) of the D3 enzyme. The time lag between the effect of GH and DEX on hepatic D3 mRNA may be due to differences in the mechanism of action between both hormones, a subject that needs further investigation.