HORMONAL-REGULATION OF MICROSOMAL FLAVIN-CONTAINING MONOOXYGENASE ACTIVITY BY SEX STEROIDS AND GROWTH-HORMONE IN COCULTURED ADULT MALE-RAT HEPATOCYTES

To investigate the hormonal control of the expression of flavin-contai ning monooxygenase (FMO; EC 1.14.13.8) under defined in vitro conditio ns, adult male rat hepatocytes were isolated by collagenase perfusion and co cultured with rat liver epithelial cells of primitive biliary o rigin. The direct effect of 17 beta-estradiol, testosterone, 5 alpha-d ihydrotestosterone (5 alpha-DHT) and human growth hormone (hGH) on FMO activity was studied using this in vitro model. Optimal, non-cytotoxi c hormonal concentrations were determined by measuring the lactate deh ydrogenase (LDH) index. In addition, the microsomal protein content of the cultured hepatocytes was determined as a function of culture time . The female sex hormone 17 beta-estradiol caused a significant decrea se in FMO as a function of culture time. After 14 days of exposure, FM O activity decreased by 56%. Neither of the male sex hormones or human growth hormone had an effect on FMO activity. These results in co-cul tured male rat hepatocytes support in vivo observation that 17 beta-es tradiol is a potent hormone involved in the negative regulation of the expression of FMO in male rat liver. (C) 1998 Elsevier Science Inc.