Berg J P, Sørnes G, Torjesen P A, Haug E
Hormone Laboratory, Aker Hospital, Oslo, Norway.
Mol Cell Endocrinol. 1991 Apr;76(1-3):201-6. doi: 10.1016/0303-7207(91)90274-v.
A rat thyroid cell line (FRTL-5) was used to study the effect of cholecalciferols on cAMP production. The active cholecalciferol metabolite, calcitriol, caused a reduction in basal and thyrotropin (TSH)-stimulated cAMP production. The inhibitory effects were demonstrated after 1 and 2 days, respectively. The maximum effect on both basal and TSH-stimulated cAMP production was observed after 3-4 days of treatment. The effect was detectable at 10(-10) and maximal at 10(-8) mol/l. Calcitriol was about 300 times more potent than calcidiol in attenuating cAMP production, whereas (24R)-hydroxycalcidiol in concentrations up to 3 x 10(-8) mol/l had no effect. After removal of added calcitriol the cAMP response to TSH returned to normal within 8 days. Calcitriol (10(-8) mol/l) also inhibited cell growth. Our results show that calcitriol at physiological concentrations inhibits both basal and TSH-stimulated cAMP production in rat thyroid cells. This indicates that calcitriol may modulate the effect of TSH on thyroid function and growth.
采用大鼠甲状腺细胞系(FRTL-5)研究胆钙化醇对环磷酸腺苷(cAMP)生成的影响。活性胆钙化醇代谢产物骨化三醇可使基础状态及促甲状腺激素(TSH)刺激的cAMP生成减少,其抑制作用分别在1天和2天后显现。在处理3 - 4天后观察到对基础状态及TSH刺激的cAMP生成的最大效应。在10⁻¹⁰时可检测到该效应,在10⁻⁸mol/L时达到最大。在减弱cAMP生成方面,骨化三醇的效力比骨化二醇强约300倍,而浓度高达3×10⁻⁸mol/L的(24R)-羟基骨化二醇则无作用。去除添加的骨化三醇后,对TSH的cAMP反应在8天内恢复正常。骨化三醇(10⁻⁸mol/L)也抑制细胞生长。我们的结果表明,生理浓度的骨化三醇可抑制大鼠甲状腺细胞基础状态及TSH刺激的cAMP生成。这表明骨化三醇可能调节TSH对甲状腺功能和生长的作用。