Sex and age-related differences in aminopyrine N-demethylase activity in DA- and Wistar-strain rat liver microsomes. Effect of ovariectomy.
1. Liver microsomal mixed-function oxidase components were studied in Wistar and Dark Agouti (DA) rats (4-45 weeks) with regard to sex- and age-related differences. Total cytochrome P-450 ranged from 0.29 to 1 nmol/mg in Wistar rats and from 0.21 to 1.27 nmol/mg in DA rats, males had higher levels than females (P less than 0.0025). Cytochrome b5 ranged between 0.42-1.37 nmol/mg and 0.42-1.56 nmol/mg in Wistar and DA strains, respectively, and NADPH-reductase activity ranged between 14-43 and 11-46 nmol/min per mg (Wistar and DA respectively). 2. Significant age-related differences were found in DA rats with four- to six-fold increase in N-demethylase activity from young to adult rats. Sex-related differences were found in both Wistar- and DA-strain rats, with males having higher (about twice) metabolic activity than females. In contrast, no significant sex- or age-related differences in cytochrome b5 content, or NADPH-reductase activity, were found. 3. Ovariectomy of 10-13-week-old females did not affect N-demethylase activity, cytochrome P-450, cytochrome b5 or NADPH-reductase activity in Wistar or DA rats. 4. Cytochrome P-450 content did not correlate (r = 0.35) with aminopyrine N-demethylase activity. 5. Results indicate that sex- and age-related differences are due to changes in the isozymic composition of cytochrome P-450, and that these changes are not subject to oestrogen regulation.
García-Agúndez
J A
JA
Department of Pharmacology and Psychiatry, Medical School, University Extremadura, Badajoz, Spain.
Benítez
J
J
D000375:Aging; D000633:Aminopyrine N-Demethylase / Q000378:metabolism*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015786:Cytochromes b5 / Q000378:metabolism; D005260:Female; D008099:Liver / Q000254:growth & development*; D008862:Microsomes, Liver / Q000201:enzymology*; D010052:Ovariectomy; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics; D013045:Species Specificity
D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D000633:Aminopyrine N-Demethylase