Samuels H H, Stanley F, Casanova J
J Clin Invest. 1979 Jun;63(6):1229-40. doi: 10.1172/JCI109418.
We have previously demonstrated that L-triiodothyronine (L-T3) induces an increase in growth hormone synthesis and messenger RNA in cultured GH1 cells, a rat pituitary cell line. In addition to regulating the growth hormone response, L-T3 elicits a time- and dose-dependent reduction in the level of its nuclear receptor, which is a direct function of the occupancy of the receptor binding site. In this study we have compared the relative affinity of L-T3, triiodothyroacetic acid, D-triiodothyronine (D-T3), and L-thyroxine (L-T4) for the receptor with the induction of the growth hormone synthesis and the ability of these compounds to elicit a reduction in thyroid hormone nuclear receptor levels. Triiodothyroacetic acid and D-T3 were specifically examined because the biologic effect of these compounds in the intact rat is significantly lower than predicted by their affinity for the receptor using isolated rat liver nuclei in vitro. In intact cells each compound demonstrated an excellent relationship between the relative receptor affinity, the induction of growth hormone production, and the concentration-dependent reduction in nuclear receptor levels. With the exception of D-T3, the relative affinity of iodothyronine was identical for the receptor using intact cells in serum-free media, or isolated GH1 cell nuclei in vitro. The apparent receptor affinity of D-T3 with intact cells was 5.5-fold lower than with isolated nuclei, which suggests a decrease in cell entry of D-T3 relative to the other iodothyronines. Quantitation of the [125I]iodothyronine associated with the receptor in GH1 cells after a 36-h incubation with L-125I-T4 was 90% L-T4 and 10% L-T3, which indicates that the major effect of L-T4 in GH1 cells is a result of intrinsic L-T4 activity. Studies with dispersed rat anterior pituitary cells demonstrated that L-T3 induces growth hormone synthesis and elicits a reduction in nuclear receptor levels in the same fashion as GH1 cells. The observation that thyroid hormone influences dispersed rat pituitary cells in a fashion qualitatively similar to GH1 cells may have implications for the growth hormone response of the somatotroph cell in vivo to different thyroidal states.
我们之前已经证明，L-三碘甲状腺原氨酸（L-T3）可诱导培养的大鼠垂体细胞系GH1细胞中生长激素合成及信使核糖核酸增加。除了调节生长激素反应外，L-T3还会引起其核受体水平呈时间和剂量依赖性降低，这是受体结合位点占有率的直接作用。在本研究中，我们比较了L-T3、三碘甲状腺乙酸、D-三碘甲状腺原氨酸（D-T3）和L-甲状腺素（L-T4）对受体的相对亲和力，以及它们诱导生长激素合成的能力和引发甲状腺激素核受体水平降低的能力。对三碘甲状腺乙酸和D-T3进行了专门研究，因为这些化合物在完整大鼠体内的生物学效应明显低于根据其在体外对分离的大鼠肝细胞核的亲和力所预测的效应。在完整细胞中，每种化合物在相对受体亲和力、生长激素产生的诱导以及核受体水平的浓度依赖性降低之间都表现出良好的关系。除D-T3外，在无血清培养基中的完整细胞或体外分离的GH1细胞核中，碘甲状腺原氨酸对受体的相对亲和力相同。D-T3与完整细胞的表观受体亲和力比与分离细胞核的低5.5倍，这表明相对于其他碘甲状腺原氨酸，D-T3进入细胞的能力有所下降。用L-125I-T4孵育36小时后，GH1细胞中与受体结合的[125I]碘甲状腺原氨酸定量结果为90%是L-T4和10%是L-T3，这表明L-T4在GH1细胞中的主要作用是其内在L-T4活性的结果。对分散的大鼠垂体前叶细胞的研究表明，L-T3以与GH1细胞相同的方式诱导生长激素合成并引起核受体水平降低。甲状腺激素以与GH1细胞定性相似的方式影响分散的大鼠垂体细胞这一观察结果，可能对体内生长激素细胞对不同甲状腺状态的生长激素反应具有启示意义。
