Changes in adrenal microsomal cytochrome(s) P-450 with aging in the guinea pig

Studies were carried out to investigate the mechanism(s) responsible for the changes in adrenal microsomal mixed function oxidase activity which occur with aging (30-200 days) in guinea pigs. With aging, the rate os metabolism of xenobiotics [ethylmorphine and benzo(a)pyrene] by adrenal microsomes increased 3- to 5-fold. Steroid 17 alpha- and 21-hydroxylations, when expressed per mg protein, were similar in immature (30 days old) and mature (200 days old) animals. Adrenal microsomal NADPH- and NADH-cytochrome c reductase activities and cytochrome b5 concentrations increased wih aging, but cytochrome P-450 concentrations were not significantly different in young and old guinea pigs. Maximal type I difference spectra produced by steroids were the same in adrenal microsomes from 30- and 200-day-old guinea pigs, but the ethylmorphine-induced spectrum was far greater in the older animals. Progesterone enhanced NADPH-cytochrome P-450 reductase activity to about the same extent in adrenal microsomes from 30- and 200-day-old guinea pigs. Ethylmorphine had no effect on the rate of reduction of cytochrome P-450 in adrenals from young animals but produced a 4-fold increase in activity in adrenals from older animals. The results demonstrate selective changes in adrenal xenobiotic metabolism with aging and suggest that changes in the composition and/or reactivity of adrenal cytochromes P-450 are responsible for the effects of aging.