Inhibition of thyrotropin-induced DNA synthesis in thyroid follicular cells by microinjection of an antibody to the stimulatory G protein of adenylate cyclase, Gs.
Inhibition of thyrotropin-induced DNA synthesis in thyroid follicular cells by microinjection of an antibody to the stimulatory G protein of adenylate cyclase, Gs.
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通过显微注射腺苷酸环化酶刺激性 G 蛋白 Gs 的抗体，抑制甲状腺滤泡细胞中促甲状腺素诱导的 DNA 合成。
DOI：
10.1016/s0021-9258(18)42200-4
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
G. Burrow
中科院分区：
文献类型：
--
作者：
J. Meinkoth;P. Goldsmith;A. Spiegel;J. Feramisco;G. Burrow
促甲状腺激素（TSH）是甲状腺滤泡细胞的重要调节因子。虽然它在维持分化功能中的作用是无可争议的，但它作为有丝分裂原的作用却不太清楚。在一些细胞中，TSH诱导DNA合成和细胞增殖，而在其他细胞中，TSH仅在存在额外的生长因子（如胰岛素样生长因子-1）时才有丝分裂。TSH引起细胞内cAMP升高，并被认为在其有丝分裂作用中利用这种第二信使系统。我们在Wistar大鼠甲状腺细胞（WRT）中研究了TSH作为丝裂原的作用（Brandi, m.l, Rotella, c.m, Mavilia， C, Franceschelli， F., Tanini, a ., and Toccafondi， R., 1987）。内分泌，54,91-103)，并检查了鸟嘌呤核苷酸结合蛋白Gs在其有丝分裂作用中的作用。WRT细胞合成DNA响应TSH和cAMP的升高。此外，TSH引起了一个指示基因的快速刺激，该基因的表达受cAMP反应元件的调节。微量注射针对Gs蛋白的抑制多克隆抗体后，tsh诱导的基因表达和DNA合成变化均显著降低。这些结果表明，几乎所有TSH的有丝分裂作用都是通过WRT细胞中的Gs蛋白转导的，可能是通过腺苷酸环化酶的调节。TSH的全部或部分作用是由cAMP和cAMP依赖性蛋白激酶介导的，仍有待确定。
Thyrotropin (TSH) is an important regulator of thyroid follicular cells. While its role in the maintenance of differentiated functions is undisputed, its role as a mitogen is less clear. TSH induces DNA synthesis and cell proliferation in some cells, while in others, TSH is mitogenic only in the presence of additional growth factors such as insulin-like growth factor-1. TSH causes elevations in intracellular cAMP and is thought to utilize this second messenger system in its mitogenic action. We studied TSH as a mitogen in Wistar rat thyroid cells (WRT) (Brandi, M. L., Rotella, C. M., Mavilia, C., Franceschelli, F., Tanini, A., and Toccafondi, R. (1987) Mol. Cell. Endocrinol. 54, 91-103) and examined the role of the guanine nucleotide binding protein, Gs, in its mitogenic action. WRT cells synthesized DNA in response to TSH and elevations in cAMP. In addition, TSH caused a rapid stimulation of an indicator gene whose expression is regulated by cAMP response elements. Following microinjection of an inhibitory polyclonal antibody raised against the Gs protein, both TSH-induced changes in gene expression and DNA synthesis were significantly reduced. These results demonstrate that virtually all of the mitogenic action of TSH is transduced through the Gs protein in WRT cells, presumably through the regulation of adenylate cyclase. Whether all or only part of TSH action is mediated by cAMP and the cAMP-dependent protein kinase remains to be determined.