Developmental regulation of flavin-containing monooxygenase form 1 in the liver and kidney of fetal and neonatal rabbits.
Flavin-containing monooxygenases (FMOs) comprise a multi-gene family and catalyze the oxygenation of soft nucleophilic sulfur, nitrogen, phosphorus, and selenium in xenobiotics. Previous studies have demonstrated that FMO is regulated developmentally and by the administration of certain steroid hormones. This study examined the expression of FMO form 1 in the livers and kidneys of fetal and neonatal rabbits, from day 25 of gestation through 3 weeks of age, by assaying FMO1 mRNA and protein levels, as well as catalytic activity. FMO1 mRNA and protein expression and FMO catalytic activity were present in fetal livers at the earliest time point measured (day 25 of gestation), although at levels approximately 10% of that found in adult livers. Hepatic FMO1 mRNA levels increased during and after gestation; levels were not significantly different from those measured in adult male livers. FMO1 protein content and activity rose rapidly after birth to reach 70-80% of adult levels by 3 weeks of age. The expression of FMO1 in fetal and neonatal kidneys was markedly lower than in liver. FMO1 mRNA levels never averaged more than 3.4% of adult male liver levels, but did not differ from adult kidney levels at any of the points measured. Protein levels and enzyme activity rose significantly after birth to approximately 30% of the level in adult kidneys by 3 weeks of age. The early developmental appearance of FMO1 suggests a possible role in the metabolism of xenobiotics through transplacental or lactational exposures.
Larsen-Su
Shelley A
SA
Department of Environmental and Molecular Toxicology, The Linus Pauling Institute, Oregon State University, 1007 ALS, Corvallis, OR 97331, USA.
Krueger
Sharon K
SK
Yueh
Mei Fei
MF
Pereira
Clifford B
CB
Williams
David E
DE
D000818:Animals; D005314:Embryonic and Fetal Development; D005260:Female; D005333:Fetus / Q000201:enzymology; D007668:Kidney / Q000196:embryology / Q000201:enzymology*; D008099:Liver / Q000196:embryology / Q000201:enzymology*; D008431:Maternal-Fetal Exchange; D010105:Oxygenases / Q000378:metabolism*; D011247:Pregnancy; D011817:Rabbits
D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)