Levine M A, Feldman A M, Robishaw J D, Ladenson P W, Ahn T G, Moroney J F, Smallwood P M
Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
J Biol Chem. 1990 Feb 25;265(6):3553-60.
We have studied the influence of thyroid hormone status in vivo on expression of the genes encoding guanine nucleotide-binding regulatory protein (G protein) alpha-subunits Gs alpha, Gi alpha(2), Gi alpha(3), and both the 36-kDa form (beta 1) and the 35-kDa form (beta 2) of the beta-subunit in rat ventricle. The relative amounts of immunoactive Gi alpha(2) and Gi alpha(3) were greater in ventricular membranes from hypothyroid animals than from euthyroid animals (1.9- and 2.6-fold, respectively). A corresponding 2.3-fold increase in Gi alpha(2) mRNA was observed as well as a 1.5-fold increase in Gi alpha(3) mRNA. The relative amounts of immunoactive beta 1 and beta 2 polypeptides were also increased (2.8- and 1.8-fold, respectively) in the hypothyroid state and corresponded with comparable increases in the relative levels of beta 1 and beta 2 mRNAs. No difference was seen between the amounts of Gi alpha(2), Gi alpha(3), beta 1, and beta 2 in the euthyroid state and the hyperthyroid state. In contrast to these effects of thyroid hormone status on Gi alpha and beta, the steady-state amounts of Gs alpha protein and mRNA were not altered by thyroid hormone status. Thyroid hormone status did not alter sensitivity of adenylyl cyclase to stimulation by sodium fluoride or guanyl-5'-yl imidodiphosphate (GppNHp), nor did it influence GppNHp-induced inhibition of forskolin-stimulated enzyme activity. These results demonstrate that thyroid hormone status in vivo can regulate expression of specific G protein subunits in rat myocardium. However, the physiological consequences of these changes remain unclear.
我们研究了体内甲状腺激素状态对大鼠心室中编码鸟嘌呤核苷酸结合调节蛋白（G蛋白）α亚基Gsα、Giα(2)、Giα(3)以及β亚基36 kDa形式（β1）和35 kDa形式（β2）的基因表达的影响。甲状腺功能减退动物心室膜中免疫活性Giα(2)和Giα(3)的相对含量高于甲状腺功能正常的动物（分别为1.9倍和2.6倍）。观察到Giα(2) mRNA相应增加2.3倍，Giα(3) mRNA增加1.5倍。甲状腺功能减退状态下免疫活性β1和β2多肽的相对含量也增加（分别为2.8倍和1.8倍），且与β1和β2 mRNA相对水平的相应增加一致。甲状腺功能正常状态和甲状腺功能亢进状态下Giα(2)、Giα(3)、β1和β2的含量没有差异。与甲状腺激素状态对Giα和β的这些影响相反，甲状腺激素状态不会改变Gsα蛋白和mRNA的稳态含量。甲状腺激素状态不会改变腺苷酸环化酶对氟化钠或鸟苷-5'-基亚氨基二磷酸（GppNHp）刺激的敏感性，也不会影响GppNHp对福斯可林刺激的酶活性的抑制作用。这些结果表明，体内甲状腺激素状态可以调节大鼠心肌中特定G蛋白亚基的表达。然而，这些变化的生理后果仍不清楚。
