Barlow J W, Crowe T C, Cowen N L, Raggatt L E, Topliss D J, Blok R B, Stockigt J R
Ewen Downie Metabolic Unit, Alfred Hospital, Melbourne, Victoria, Australia.
Eur J Endocrinol. 1994 Feb;130(2):166-70. doi: 10.1530/eje.0.1300166.
We examined the time course and dose response of the triiodothyronine (T3) effect on mRNAs for sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) in cells of the human hepatoma line HepG2. After 7 h of exposure to a saturating dose of T3, SHBG mRNA was unchanged but increased to 1.5 +/- 0.1 times the unstimulated control at 22 h. Maximal stimulation (2.3 +/- 0.6) was observed at 2-3 days. Corticosteroid-binding globulin mRNA was unchanged for 22 h after exposure to T3 but diminished thereafter to 64% by day 3. At 3-4 days of exposure, the changes in both SHBG mRNA and CBG mRNA were dose-responsive to the T3 concentration. For both mRNAs, half-maximal response occurred between 10 and 20 pmol/l bioavailable T3. Cortisol-binding proteins secreted by HepG2 cells after 3 days in culture also were T3 dose-responsive. No re-uptake of secreted CBG by the cells was observed, suggesting that the T3 effect on CBG secretion occurs during production of the mature protein. These data suggest that T3 stimulates the expression of the SHBG gene and attenuates the expression of the CBG gene. The effects of T3 on these genes are consistent with the increase in circulating SHBG and decrease in circulating CBG observed in hyperthyroidism. The HepG2 cells may be a useful human cell line in which to study the diversity of the molecular mechanisms of T3 action.
我们研究了三碘甲状腺原氨酸（T3）对人肝癌细胞系HepG2中与性激素结合球蛋白（SHBG）和皮质类固醇结合球蛋白（CBG）相关的mRNA的时间进程和剂量反应。在暴露于饱和剂量的T3 7小时后，SHBG mRNA没有变化，但在22小时时增加到未刺激对照的1.5±0.1倍。在2 - 3天时观察到最大刺激（2.3±0.6）。暴露于T3后22小时内，皮质类固醇结合球蛋白mRNA没有变化，但此后到第3天时减少到64%。在暴露3 - 4天时，SHBG mRNA和CBG mRNA的变化对T3浓度均呈剂量反应。对于这两种mRNA，半数最大反应发生在生物可利用T3浓度为10至20 pmol/l之间。培养3天后HepG2细胞分泌的皮质醇结合蛋白也对T3呈剂量反应。未观察到细胞对分泌的CBG的再摄取，这表明T3对CBG分泌的影响发生在成熟蛋白的产生过程中。这些数据表明，T3刺激SHBG基因的表达并减弱CBG基因的表达。T3对这些基因的作用与甲状腺功能亢进时循环中SHBG增加和CBG减少一致。HepG2细胞可能是一种有用的人类细胞系，可用于研究T3作用分子机制的多样性。
