Selzer E, Wilfing A, Schiferer A, Hermann M, Grubeck-Loebenstein B, Freissmuth M
Institute of Pharmacology, University of Vienna, Austria.
Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1609-13. doi: 10.1073/pnas.90.4.1609.
The alpha subunits of the stimulatory and inhibitory G proteins, Gs alpha and Gi alpha, activate transmembrane-signaling systems involved in the control of cell proliferation. We have investigated the pattern of expression of Gi alpha subtypes and Gi alpha-mediated proliferative responses in the human thyroid. Human thyroid membranes contain two subtypes of Gi alpha, Gi alpha-1 and Gi alpha-2, as assessed by using specific antibodies. The expression of Gi alpha-1 is under tight control by thyrotropin in vivo and in primary cultures of thyroid epithelial cells. In contrast, Gi alpha-1 is expressed in the absence of thyrotropin in thyroid autonomous adenoma, an endocrine-active tumor, and its levels are not regulated by thyrotropin in thyroid epithelial cells prepared from these tumors. If thyroid epithelial cells are treated with pertussis toxin to block signal transduction via Gi, the mitogenic response to serum factors is reduced. These observations demonstrate that Gi subtypes transmit growth stimuli in the human thyroid. The constitutive expression of Gi alpha-1 in autonomous adenoma may allow for the unregulated stimulation of thyroid cell proliferation by a yet unidentified signaling pathway and, thus, be causally related to autonomous growth of thyroid cells.
刺激性G蛋白和抑制性G蛋白的α亚基，即Gsα和Giα，可激活参与细胞增殖调控的跨膜信号系统。我们研究了Giα亚型的表达模式以及Giα介导的人甲状腺增殖反应。通过使用特异性抗体评估，人甲状腺膜含有两种Giα亚型，即Giα-1和Giα-2。在体内和甲状腺上皮细胞原代培养中，Giα-1的表达受到促甲状腺激素的严格控制。相比之下，在自主性甲状腺腺瘤（一种内分泌活性肿瘤）中，即使没有促甲状腺激素，Giα-1也会表达，并且在从这些肿瘤制备的甲状腺上皮细胞中，其水平不受促甲状腺激素的调节。如果用百日咳毒素处理甲状腺上皮细胞以阻断通过Gi的信号转导，对血清因子的促有丝分裂反应就会降低。这些观察结果表明，Gi亚型在人甲状腺中传递生长刺激信号。Giα-1在自主性腺瘤中的组成性表达可能允许通过尚未确定的信号通路对甲状腺细胞增殖进行不受调控的刺激，因此，与甲状腺细胞的自主性生长有因果关系。
