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促甲状腺激素在表达人促甲状腺激素受体cDNA的中国仓鼠卵巢细胞中激活环磷酸腺苷和磷脂酰肌醇-4,5-二磷酸信号级联反应。

Thyrotropin activates both the cyclic AMP and the PIP2 cascades in CHO cells expressing the human cDNA of TSH receptor.

作者信息

Van Sande J, Raspé E, Perret J, Lejeune C, Maenhaut C, Vassart G, Dumont J E

机构信息

Institute of Interdisciplinary Research, University of Brussels, School of Medicine, Belgium.

出版信息

Mol Cell Endocrinol. 1990 Nov 12;74(1):R1-6. doi: 10.1016/0303-7207(90)90209-q.

DOI:10.1016/0303-7207(90)90209-q
PMID:2178105
Abstract

The effect of thyrotropin (TSH) on cyclic AMP accumulation, phosphatidylinositol bisphosphate (PIP2) hydrolysis and [Ca2+]i rise has been studied in CHO cells stably transfected with human TSH receptor (hTSHR) cDNA. In human thyroid slices, TSH activates these two intracellular cascades with a higher affinity for the adenylate cyclase activation (from 0.1 to 1 mU/ml TSH) than for phospholipase C activation (from 1 to 10 mU/ml TSH). The CHO cells transfected with the recently cloned cDNA of human TSH receptor respond in the same way to TSH. They respond between 0.1 and 1 mU/ml TSH for cyclic AMP accumulation and between 1 and 10 mU/ml TSH for inositol monophosphate (IP1) increase. In these same cells, TSH 10 mU/ml, but not forskolin (10 microM), or dibutyryl cyclic AMP (100 microM), clearly enhances intracellular calcium concentration [( Ca2+]i). Our results demonstrate unequivocally that a single transcription unit has the potential to encode receptor molecules coupled to both cascades.

摘要

已在稳定转染人促甲状腺激素受体(hTSHR)cDNA的CHO细胞中研究了促甲状腺激素(TSH)对环磷酸腺苷(cAMP)积累、磷脂酰肌醇二磷酸(PIP2)水解和细胞内钙离子浓度升高([Ca2+]i)的影响。在人甲状腺切片中,TSH激活这两条细胞内信号级联反应,对腺苷酸环化酶激活的亲和力更高(TSH浓度为0.1至1 mU/ml),而对磷脂酶C激活的亲和力较低(TSH浓度为1至10 mU/ml)。用最近克隆的人促甲状腺激素受体cDNA转染的CHO细胞对TSH的反应方式相同。它们对cAMP积累的反应TSH浓度在0.1至1 mU/ml之间,对肌醇单磷酸(IP1)增加的反应TSH浓度在1至10 mU/ml之间。在这些相同的细胞中,10 mU/ml的TSH能明显提高细胞内钙浓度([Ca2+]i),而10 μM的福斯高林或100 μM的二丁酰环磷腺苷则不能。我们的结果明确表明,单个转录单元有可能编码与这两条信号级联反应都偶联的受体分子。

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