J. Biochem, 1988, Vol. 104, No. 5 785-790
© 1988 Japanese Biochemical Society
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A Sex-Specific Form of Cytochrome P-450 Catalyzing Propoxycoumarin O-Depropylation and Its Identity with Testosterone 6ß-Hydroxylase in Untreated Rat Livers: Reconstitution of the Activity with Microsomal Lipids1
*Department of Pharmacology, School of Medicine, Keio University Shinjuku-ku, Tokyo 160
**Laboratory of Chemistry, Osaka City University Medical School Abeno-ku, Osaka, Osaka 545
2 To whom correspondence should be addressed
Characteristics of a typical male-dominant reaction, dealkylation of n-propoxycoumarin, in rat livers were studied in relation to microsomal testosterone 6ß-hydroxylase. The depropylation was more than 10-fold higher in the liver of male than female adult rats, but the sex-related difference was eliminated by neonatal castration. Hypophysectomy of adult male rats, which decreased the rates of male-specific P-450-male-dependent reactions, increased the depropylation of propoxycoumarin, while the rate was decreased by either intermittent injection or continuous infusion of human growth hormone to hypophysectomized rats. With regard to age-related difference, microsomal depropylation was detectable at neonate and reached a maximal level at 14 to 20d of age, but was abruptly diminished only in female rats at puberty. These changes are in good agreement with those of testosterone 6ß-hydroxylation and the content of a male-specific P-4506ß–1/PB-1. In reconstituted systems using extracted microsomal lipids, P-4506ß–1/PB-1 and P-450-male catalyzed the depropylation of propoxycoumarin. However, the microsomal depropylation was inhibited by antibodies which recognize P-4506ß–1/PB-1 but not P-450-male. These results indicate that microsomal depropylation of propoxycoumarin is catalyzed mainly by a male-specific P-4506ß–1/PB-1 in livers of untreated rats.
1 This work was supported in part by a Grant-in-Aid from the Ministry of Education, Science and Culture of Japan.
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