ABSTRACT
Here, we have found that type 2 iodothyronine deiodinase (D2) is present in rat aorta media and that there is a circadian variation in the D2 expression. The D2 mRNA was approximately 4-fold higher at 0900 h than at 2100 h, and the activity was approximately 6-fold higher at noon than at 2100 h. The increase in aorta media D2 activity is preceded by the increase in its mRNA. The increase in D2 mRNA and activity in the circadian variation was reduced by the administration of prazosin, an alpha1-adrenergic antagonist, and propranolol, a beta- adrenergic antagonist. Furthermore, phenylephrine, an alpha1-adrenergic agonist, and isoproterenol, a beta-adrenergic agonist, caused a significant increase in D2 mRNA and activity. In the hypothyroid rats, aorta mediae D2 mRNA at both 0900 and 2100 h were not significantly different when compared with those in the euthyroid rats. On the other hand, aorta mediae D2 activity at both 1200 and 2100 h in the hypothyroid rats were approximately 2-fold higher. From these results, we suggest that D2 activity of rat aorta media is increased by both alpha1- and beta-adrenergic stimulation, at least partly, at the pretranslational level. We also suggest that both alpha1- and beta-adrenergic mechanisms may be involved, at least partly, in the circadian variation of the activity. In the hypothyroid state, the aorta media D2 activity is increased mainly by the posttranslational mechanism, and the similar circadian variation of the D2 expression is present as in the euthyroid state.
Subject(s)
Aorta/enzymology , Hypothyroidism/physiopathology , Iodide Peroxidase/genetics , Adrenergic alpha-Antagonists/pharmacology , Adrenergic beta-Antagonists/pharmacology , Animals , Gene Expression Regulation, Enzymologic/drug effects , Male , Prazosin/pharmacology , Propranolol/pharmacology , RNA, Messenger/analysis , Rats , Rats, Sprague-Dawley , Receptors, Adrenergic, alpha-1/metabolism , Receptors, Adrenergic, beta/metabolism , Thyroxine/blood , Triiodothyronine/blood , Tunica Media/enzymology , Yohimbine/pharmacology , Iodothyronine Deiodinase Type IIABSTRACT
Type 2 deiodinase (D2) catalyzes the conversion of the prohormone T4 to the biologically active T3. D2 is expressed in human aortic smooth muscle cells (hASMCs). In this study, we demonstrated that the D2 mRNA and activity in hASMCs were up-regulated by platelet-derived growth factor-BB (PDGF-BB) and basic fibroblast growth factor (bFGF). The induction of D2 mRNA by PDGF-BB and bFGF was dependent on de novo RNA and protein synthesis. PD98059, a specific inhibitor of the upstream kinase that activates extracellular signal-regulated kinase (ERK), significantly suppressed the induction by both PDGF-BB and bFGF. SB203580, a specific inhibitor of p38 mitogen-activated protein (MAP) kinase, and SP600125, a specific inhibitor of c-Jun N-terminal kinase (JNK), also reduced the induction by both PDGF-BB and bFGF. These results suggest that both PDGF-BB and bFGF induce D2 expression at least partly via ERK pathway. The p38 MAP kinase and JNK pathways may also be involved in the induction.
