Sex and age-related differences in aminopyrine N-demethylase activity in DA- and Wistar-strain rat liver microsomes. Effect of ovariectomy

Abstract

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<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 ₅ 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.