Dremier S, Coulonval K, Perpete S, Vandeput F, Fortemaison N, Van Keymeulen A, Deleu S, Ledent C, Clément S, Schurmans S, Dumont J E, Lamy F, Roger P P, Maenhaut C
Institute of Interdisciplinary Research (IRIBHN), Université of Brussels, School of Medicine, Campus Erasme, B 1070 Brussels, Belgium.
Ann N Y Acad Sci. 2002 Jun;968:106-21. doi: 10.1111/j.1749-6632.2002.tb04330.x.
Cyclic AMP has been shown to inhibit cell proliferation in many cell types and to activate it in some. The latter has been recognized only lately, thanks in large part to studies on the regulation of thyroid cell proliferation in dog thyroid cells. The steps that led to this conclusion are outlined. Thyrotropin activates cyclic accumulation in thyroid cells of all the studied species and also phospholipase C in human cells. It activates directly cell proliferation in rat cell lines, dog, and human thyroid cells but not in bovine or pig cells. The action of cyclic AMP is responsible for the proliferative effect of TSH. It accounts for several human diseases: congenital hyperthyroidism, autonomous adenomas, and Graves' disease; and, by default, for hypothyroidism by TSH receptor defect. Cyclic AMP proliferative action requires the activation of protein kinase A, but this effect is not sufficient to explain it. Cyclic AMP action also requires the permissive effect of IGF-1 or insulin through their receptors, mostly as a consequence of PI3 kinase activation. The mechanism of these effects at the level of cyclin and cyclin-dependent protein kinases involves an induction of cyclin D3 by IGF-1 and the cyclic AMP-elicited generation and activation of the cyclin D3-CDK4 complex.
环磷酸腺苷（cAMP）已被证明在许多细胞类型中可抑制细胞增殖，而在某些细胞类型中则可激活细胞增殖。后者直到最近才被认识到，这在很大程度上要归功于对犬甲状腺细胞中甲状腺细胞增殖调节的研究。本文概述了得出这一结论的步骤。促甲状腺激素可激活所有研究物种甲状腺细胞中的cAMP循环积累，也可激活人细胞中的磷脂酶C。它可直接激活大鼠细胞系、犬和人甲状腺细胞中的细胞增殖，但对牛或猪细胞则无此作用。cAMP的作用是促甲状腺激素（TSH）增殖效应的原因。它可导致多种人类疾病：先天性甲状腺功能亢进、自主性腺瘤和格雷夫斯病；反之，也可导致TSH受体缺陷引起的甲状腺功能减退。cAMP的增殖作用需要蛋白激酶A的激活，但这种效应不足以解释其全部作用。cAMP的作用还需要胰岛素样生长因子-1（IGF-1）或胰岛素通过其受体产生的允许作用，这主要是PI3激酶激活的结果。在细胞周期蛋白和细胞周期蛋白依赖性蛋白激酶水平上，这些效应的机制涉及IGF-1诱导细胞周期蛋白D3以及cAMP引发的细胞周期蛋白D3-CDK4复合物的生成和激活。
