EFFECT OF THYROID-HORMONES ON FLAVIN-CONTAINING MONOOXYGENASE ACTIVITY IN COCULTURED ADULT-RAT HEPATOCYTES

The regulation of flavin-containing monooxygenase (FMO) by thyroid hor mones was examined under well defined in vitro conditions using adult male rat hepatocytes co-cultured with rat liver epithelial cells of pr imitive biliary origin. Serum free medium was used to avoid interferen ces from foetal bovine serum. The effect of thyroxine (T4) and its maj or metabolite L-triiodothyronine (T3) on FMO activity was estimated sp ectrophotometrically by measuring the rate of methimazole oxygenation. The highest non-cytotoxic doses of T3 and T4 that could be used in co -cultures were determined by measuring both lactate dehydrogenase leak age into the medium and microsomal protein content of the hepatocytes as a function of culture rime. In addition, hormonal responsiveness of the vitro system used was confirmed by malic enzyme activity measurem ents. Administration of 10 mu M T3 or T4 was found to cause a signific ant decrease in FMO activity and content, suggesting a suppressive rol e of both hormones on the regulation of FMO activity in male rats. (C) 1998 Elsevier Scieilce Ltd. Ail rights reserved.