Kanri R, Takiyama Y, Makino I
Second Department of Internal Medicine, Asahikawa Medical College, Japan.
Thyroid. 1996 Oct;6(5):467-74. doi: 10.1089/thy.1996.6.467.
The effects of bile acids on iodide uptake and DNA synthesis were studied in cultured porcine thyroid cells. All five bile acids, which are commonly found in serum, chenodeoxycholic acid (CDCA), cholic acid (CA), deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) dose-dependently inhibited both basal and TSH-induced iodide uptake at concentrations of 25-250 microM. Since CDCA is one of the two major primary endogenous bile acids, were studied mainly the effects of CDCA. The inhibitory effect of CDCA was detected after 24 h treatment of thyroid cells, and was dependent on the time of exposure up to 72 h. Treatment of thyroid cells with CDCA for 72 h inhibited cAMP production stimulated by 50 mU/L TSH or 0.5 mg/L forskolin and also inhibited iodide uptake induced by 0.5 mM 8-bromo cAMP or 0.5 mg/L forskolin. These results suggest that CDCA inhibits iodide uptake by decreasing cAMP production as well as post-cAMP generation. Bile acids except LCA stimulated [3H]thymidine incorporation into the thyroid cells by itself, indicating that the inhibitory effect of bile acids on iodide uptake is not due to cytotoxic effect. In conclusion, these findings suggest that the direct inhibition of thyroid function by bile acids might cause hypothyroidism in chronic liver disease.
在培养的猪甲状腺细胞中研究了胆汁酸对碘摄取和DNA合成的影响。血清中常见的所有五种胆汁酸，即鹅去氧胆酸（CDCA）、胆酸（CA）、脱氧胆酸（DCA）、石胆酸（LCA）和熊去氧胆酸（UDCA），在25 - 250 microM浓度下均呈剂量依赖性地抑制基础和促甲状腺激素（TSH）诱导的碘摄取。由于CDCA是两种主要的内源性初级胆汁酸之一，因此主要研究了CDCA的作用。在甲状腺细胞经24小时处理后检测到CDCA的抑制作用，并且该作用在长达72小时的暴露时间内具有依赖性。用CDCA处理甲状腺细胞72小时可抑制由50 mU/L TSH或0.5 mg/L福司可林刺激的环磷酸腺苷（cAMP）生成，并且还抑制由0.5 mM 8 - 溴环磷酸腺苷或0.5 mg/L福司可林诱导的碘摄取。这些结果表明，CDCA通过降低cAMP生成以及cAMP生成后阶段来抑制碘摄取。除LCA外的胆汁酸自身刺激甲状腺细胞掺入[3H]胸腺嘧啶核苷，表明胆汁酸对碘摄取的抑制作用不是由于细胞毒性作用。总之，这些发现表明胆汁酸对甲状腺功能的直接抑制可能导致慢性肝病中的甲状腺功能减退。
