A sex-specific form of cytochrome P-450 catalyzing propoxycoumarin O-depropylation and its identity with testosterone 6 beta-hydroxylase in untreated rat livers: reconstitution of the activity with microsomal lipids.
Characteristics of a typical male-dominant reaction, dealkylation of n-propoxycoumarin, in rat livers were studied in relation to microsomal testosterone 6 beta-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 20 d of age, but was abruptly diminished only in female rats at puberty. These changes are in good agreement with those of testosterone 6 beta-hydroxylation and the content of a male-specific P-450(6)beta-1/PB-1. In reconstituted systems using extracted microsomal lipids, P-450(6)beta-1/PB-1 and P-450-male catalyzed the depropylation of propoxycoumarin. However, the microsomal depropylation was inhibited by antibodies which recognize P-450(6)beta-1/PB-1, but not P-450-male. These results indicate that microsomal depropylation of propoxycoumarin is catalyzed mainly by a male-specific P-450(6)beta-1/PB-1 in livers of untreated rats.
Yamazoe
Y
Y
Department of Pharmacology, School of Medicine, Keio University, Tokyo.
Murayama
N
N
Shimada
M
M
Yamauchi
K
K
Nagata
K
K
Imaoka
S
S
Funae
Y
Y
Kato
R
R
D015660:7-Alkoxycoumarin O-Dealkylase; D000375:Aging / Q000502:physiology; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology; D007016:Hypophysectomy; D008055:Lipids / Q000494:pharmacology; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009919:Orchiectomy; D010052:Ovariectomy; D010105:Oxygenases / Q000378:metabolism*; D051381:Rats; D012737:Sex Factors; D013250:Steroid Hydroxylases / Q000378:metabolism*; D013739:Testosterone / Q000494:pharmacology
D008055:Lipids; D013739:Testosterone; D013006:Growth Hormone; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D013250:Steroid Hydroxylases; D015660:7-Alkoxycoumarin O-Dealkylase; C022657:steroid hormone 6-beta-hydroxylase