三碘甲状腺氨酸影响甲状腺激素的可变剪接受体αmRNA。
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Timmer, O,他Wiersinga WM
三碘甲状腺氨酸影响甲状腺激素的可变剪接受体αmRNA。
J性。2003年11月,179(2):217 - 25所示。
- PubMed ID
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14596673 (在PubMed]
- 文摘
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c-erbAalpha基因编码两个甲状腺激素受体,TRalpha1 TRalpha2,产生的可变剪接TRalpha pre-mRNA。TRalpha2不能绑定三碘甲状腺氨酸(T(3))和TRs充当一个弱的对手。有人建议,平衡的TRalpha1 TRalpha2维持体内平衡是很重要的。在这里,我们研究甲状腺激素的影响的拼接TRalpha HepG2细胞在不同的条件下。首先,T(3)被添加到HepG2细胞内生TRalpha表达。这导致减少TRalpha1: TRalpha2 mRNA比例后的10 (-)(8)M - 10 (-) (7) M T (3)。然后,HepG2细胞孵化与血清甲状腺和甲状腺亢进的病人。血清甲状腺亢进患者(n = 6)减少TRalpha1: TRalpha2比率与HepG2细胞孵化与euthyroid患者血清(n = 8)。血清甲状腺患者(n = 6)没有影响TRalpha1: TRalpha2比例但补充和T(3)比率下降引起的。最后,我们测试了从nonthyroidal疾病患者血清(NTI; n=17) which showed no effect on TRalpha splicing when compared with controls. Free thyroxine levels in sera from hypo-, eu-, and hyperthyroid patients, but not that of NTI patients, were negatively correlated (P<0.01) to the TRalpha1:TRalpha2 ratio. We next studied the expression of the splicing factors hnRNP A1 and ASF/SF2 (SF2) in relation to the splicing of the TRalpha gene. In HepG2 cells incubated with NTI sera a negative relationship was found between the ratio of hnRNP A1:SF2 and the TRalpha1:TRalpha2 ratio. A high hnRNP A1:SF2 ratio is associated with the use of the distal 5'-splice site. The splicing direction should then change towards TRalpha2, which is indeed the case. Rev-ErbA, which is partly complementary to TRalpha2 and could therefore interfere in the splicing process, did not relate to the TRalpha1:TRalpha2 ratio. In conclusion, high T(3) levels induce a low TRalpha1:TRalpha2 ratio which could protect the cell from excessive T(3)-induced gene expression. In vivo, this might be a mechanism to keep tIssues relatively euthyroid during high serum T(3) levels.