Investigation of mecnanism to regulate intracellular T3 level by iodothyronine deiodinse

2型脱碘酶（D2）催化激素原T4转化为具有生物活性的T3。D2在人主动脉平滑肌细胞（hASMCs）中表达。检测血小板源性生长因子（PDGF）和碱性成纤维细胞生长因子（bFGF）对hASMCs D2表达的影响。PDGF或bFGF处理后D2 mRNA和活性均显著升高。PDGF和bFGF对D2 mRNA的诱导依赖于从头RNA和蛋白质合成，因为对mRNA的诱导作用被放线菌素D或放线菌酮完全阻断。此外，PD 98059（一种MEK和Erk信号级联的特异性抑制剂）阻止了PDGF和bFGF的作用。这些研究表明PDGF和bFGF主要在翻译前水平调节D2的表达。此外，PDGF和bFGF对D2表达的刺激作用似乎至少部分地由MEK/Erk信号级联的激活介导。

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). The effects of platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) on D2 expression in hASMCs were examined. D2 mRNA and activities increased markedly by treatment with PDGF or bFGF. The induction of D2 mRNA by PDGF and bFGF was dependent on de novo RNA and protein synthesis, as the inductive effect on mRNA is completely blocked by actinomycin D or cycloheximide. In addition, the effects of PDGF and bFGF were prevented by PD 98059, a specific inhibitor of MEK and the Erk signaling cascade. These studies demonstrate that PDGF and bFGF regulate D2 expression mainly at pretranslational leve. In addition, the stimulatory effects of PDGF and bFGF on D2 expression appear to be mediated at least in part by activation of the MEK/Erk signaling cascade.