THYROID EXPRESSION OF AN A2 ADENOSINE RECEPTOR TRANSGENE INDUCES THYROID HYPERPLASIA AND HYPERTHYROIDISM
THYROID EXPRESSION OF AN A2 ADENOSINE RECEPTOR TRANSGENE INDUCES THYROID HYPERPLASIA AND HYPERTHYROIDISM
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DOI：
10.1002/j.1460-2075.1992.tb05084.x
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发表时间：
1992-02-01
期刊：
影响因子：
11.4
通讯作者：
PARMENTIER, M
中科院分区：
文献类型：
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作者：
LEDENT, C;DUMONT, JE;PARMENTIER, M
环AMP （cAMP）是促甲状腺激素（TSH）作用于甲状腺细胞的主要细胞内第二信使。它能刺激培养的甲状腺细胞的生长、功能和分化。腺苷A2受体通过偶联刺激G蛋白（Gs）激活腺苷酸环化酶，已被证明在转染到各种细胞类型时可促进cAMP级联的组成性激活。为了测试A2受体是否能够在体内发挥类似的功能，并研究甲状腺细胞中永久腺苷酸环化酶激活的可能后果，在牛甲状腺球蛋白基因启动子的控制下，产生了表达犬A2腺苷受体的转基因小鼠系。A2腺苷受体转基因的甲状腺特异性表达促进了腺体增生和严重的甲状腺功能亢进，导致动物过早死亡。由此产生的甲状腺代表了一个功能亢进的腺瘤模型：它表明，在这种分化的上皮细胞中，cAMP级联的组成性激活足以刺激自主和不受控制的功能和生长。
Cyclic AMP (cAMP) is the major intracellular second messenger of thyrotropin (TSH) action on thyroid cells. It stimulates growth as well as the function and differentiation of cultured thyrocytes. The adenosine A2 receptor, which activates adenylyl cyclase via coupling to the stimulating G protein (Gs), has been shown to promote constitutive activation of the cAMP cascade when transfected into various cell types. In order to test whether the A2 receptor was able to function similarly in vivo and to investigate the possible consequences of permanent adenylyl cyclase activation in thyroid cells, lines of transgenic mice were generated expressing the canine A2 adenosine receptor under control of the bovine thyroglobulin gene promoter. Thyroid-specific expression of the A2 adenosine receptor transgene promoted gland hyperplasia and severe hyperthyroidism causing premature death of the animals. The resulting goitre represents a model of hyperfunctioning adenomas: it demonstrates that constitutive activation of the cAMP cascade in such differentiated epithelial cells is sufficient to stimulate autonomous and uncontrolled function and growth.