Coordinated maternal imprinting and paternal genotype determined the ultimate level of hepatic cytochrome P-450 and associated monooxygenase activities.
To understand the pre- and postnatal maternal influence on hepatic drug metabolism later in adult life, we have chosen to study the mouse hybrid (129/sv x LS) offspring derived from contrasting parental lines in a designated maternal environment. Results of these studies revealed that the following: 1) sex of the offspring was the major determinant for cytochrome P-450-specific content and for the activity of aryl hydrocarbon hydroxylase, testosterone 16 alpha-hydroxylase, acetanilide hydroxylase, and NADPH-cytochrome c reductase; 2) maternal factor(s) affected cytochrome P-450-specific content and the activities of acetanilide hydroxylase and aryl hydrocarbon hydroxylase but not of testosterone 15 alpha- and 16 alpha-hydroxylases or NADPH-cytochrome c reductase; 3) superimposed upon sex and maternal determination, paternal genotype significantly contributed to adult hepatic cytochrome P-450-specific content; 4) interactions between sex of the offspring and maternal factor(s) accounted for the development of testosterone 15 alpha- and 16 alpha-hydroxylase activities later in adult life; and 5) with the exception of testosterone 16 alpha-hydroxylase activity, other yet undefined factors, including the paternal genotype, contributed to most of the measured hepatic monooxygenase activities. The mechanism of coordinated maternal imprinting and paternal genotype in determining the levels of hepatic cytochrome P-450 and its associated monooxygenase activities is discussed.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005838:Genotype; D051379:Mice; D008807:Mice, Inbred BALB C; D008862:Microsomes, Liver / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000235:genetics; D011247:Pregnancy; D012737:Sex Factors; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000235:genetics*
D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D039181:Steroid 16-alpha-Hydroxylase; C023738:acetanilide hydroxylase; C022724:testosterone 7-alpha-hydroxylase, hamster; D009251:NADPH-Ferrihemoprotein Reductase