TY - JOUR
T1 - A sex-specific form of cytochrome P-450 catalyzing propoxycoumarin O-depropylation and its identity with testosterone 6β-hydroxylase in untreated rat livers
T2 - Reconstitution of the activity with microsomal lipids
AU - Yamazoe, Yasushi
AU - Murayama, Norie
AU - Shimada, Miki
AU - Yamauchi, Kiyomi
AU - Nagata, Kiyoshi
AU - Imaoka, Susumu
AU - Funae, Yoshihiko
AU - Kato, Ryuichi
PY - 1988/11
Y1 - 1988/11
N2 - Characteristics of a typical male-dominant reaction, dealkylation of n-propoxycoumarin, in rat livers were studied in relation to microsomal testosterone 6β-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 6β-hydroxylation and the content of a male-specific P-4506β-1/PB-1. In reconstituted systems using extracted microsomal lipids, P-4506β-1/PB-1 and P-450-male catalyzed the depropylation of propoxycoumarin. However, the microsomal depropylation was inhibited by antibodies which recognize P-4506β-1/PB-1 but not P-450-male. These results indicate that microsomal depropylation of propoxycoumarin is catalyzed mainly by a male-specific P-4506β-1/PB-1 in livers of untreated rats.
AB - Characteristics of a typical male-dominant reaction, dealkylation of n-propoxycoumarin, in rat livers were studied in relation to microsomal testosterone 6β-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 6β-hydroxylation and the content of a male-specific P-4506β-1/PB-1. In reconstituted systems using extracted microsomal lipids, P-4506β-1/PB-1 and P-450-male catalyzed the depropylation of propoxycoumarin. However, the microsomal depropylation was inhibited by antibodies which recognize P-4506β-1/PB-1 but not P-450-male. These results indicate that microsomal depropylation of propoxycoumarin is catalyzed mainly by a male-specific P-4506β-1/PB-1 in livers of untreated rats.
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U2 - 10.1093/oxfordjournals.jbchem.a122550
DO - 10.1093/oxfordjournals.jbchem.a122550
M3 - Article
C2 - 3266213
AN - SCOPUS:0023739379
VL - 104
SP - 785
EP - 790
JO - Journal of Biochemistry
JF - Journal of Biochemistry
SN - 0021-924X
IS - 5
ER -