Hormonal regulation of microsomal flavin-containing monooxygenase activity by sex steroids and growth hormone in co-cultured adult male rat hepatocytes.
To investigate the hormonal control of the expression of flavin-containing monooxygenase (FMO; EC 1.14.13.8) under defined in vitro conditions, adult male rat hepatocytes were isolated by collagenase perfusion and co-cultured with rat liver epithelial cells of primitive biliary origin. The direct effect of 17beta-estradiol, testosterone, 5alpha-dihydrotestosterone (5alpha-DHT) and human growth hormone (hGH) on FMO activity was studied using this in vitro model. Optimal, non-cytotoxic hormonal concentrations were determined by measuring the lactate dehydrogenase (LDH) index. In addition, the microsomal protein content of the cultured hepatocytes was determined as a function of culture time. The female sex hormone 17beta-estradiol caused a significant decrease in FMO as a function of culture time. After 14 days of exposure, FMO activity decreased by 56%. Neither of the male sex hormones or human growth hormone had an effect on FMO activity. These results in co-cultured male rat hepatocytes support in vivo observation that 17beta-estradiol is a potent hormone involved in the negative regulation of the expression of FMO in male rat liver.
Coecke
S
S
Department of Toxicology, Vrije Universiteit Brussel, Brussels, Belgium.
Debast
G
G
Phillips
I R
IR
Vercruysse
A
A
Shephard
E A
EA
Rogiers
V
V
D000818:Animals; D018920:Coculture Techniques; D013196:Dihydrotestosterone / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D010105:Oxygenases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation / Q000502:physiology; D013256:Steroids / Q000494:pharmacology*; D013739:Testosterone / Q000494:pharmacology
D012739:Gonadal Steroid Hormones; D013256:Steroids; D013196:Dihydrotestosterone; D019382:Human Growth Hormone; D013739:Testosterone; D004958:Estradiol; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)