Abstract
Administration of [3,5-3H]δ-aminolevulinic acid to immature and adult male and female rats led to the incorporation of radioactivity into liver microsomal cytochrome P-450. A biphasic decrease was observed in the radioactivity incorporated into the hemeprotein, and the half-lives were 7-8 and 42-46 hr in all cases, suggesting that at least two forms of cytochrome P-450 exist in rat liver microsomes. The ratio of the fast-phase component to the slow-phase component was 3.4-4.4:1 in the immature and adult female and the immature male rat. This ratio changed to 1.9:1 in the adult male, indicating an age and sex difference in the ratio of the two forms of the cytochrome. Castration of the male at 4 weeks of age did not prevent the change in ratio that occurred during the next 4 weeks. However, castration of male rats at birth prevented the age-dependent change in ratio that occurred after 4 weeks of age and resulted in a biphasic turnover of cytochrome P-450 that was indistinguishable from that of the adult female rat. These changes in cytochrome P-450 were correlated with changes in the activity of liver microsomal enzymes that hydroxylate testosterone at the 7α, 16α, and 6β positions. Different ratios of activities of the three hydroxylation reactions are characteristic of the immature and adult male and female rat. Castration of male rats at birth caused the development of a female pattern of testosterone hydroxylation, whereas castration at 4 weeks of age resulted in a pattern of hydroxylation that was intermediate between the adult male and female.
ACKNOWLEDGMENT We thank Mrs. C. Chvasta for her assistance in the preparation of this manuscript.
- Copyright ©, 1975, by Academic Press, Inc.
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