EFFECT OF MORPHINE ADMINISTRATION ON THE HYDROXYLATION OF STEROID HORMONES BY RAT LIVER MICROSOMES

¹ Department of Pharmacology, National Institute of Hygienic Sciences; Department of Pharmacology, School of Medicine, Keio University, Tokyo, Japan

The effect of morphine administration on progesterone and testosterone hydroxylation by liver microsomes of male and female rats was investigated. The administration of morphine significantly decreased the content of cytochrome P-450 in male rats, but not in female rats. Progesterone and testosterone hydroxylation is markedly descreased in morphine-treated male rats, but not in the females. In agreement with those results, the magnitude of the spectral changes induced by progesterone and testosterone is decreased only in morphine-treated male rats, but not in the females. Castration in male rats decreased the magnitude of spectral changes and hydroxylating activities for progesterone and testosterone, and the administration of testosterone to castrated rats restored these values to the level observed in intact male rats. The magnitude of spectral change and hydroxylating activity for progesterone and testosterone in castrated male rats was not decreased by morphine treatment, but was markedly decreased in testosterone-treated castrated rats. Therefore, the ratios of the hydroxylating activity for progesterone and testosterone to the magnitude of the spectral changes are not significantly affected in morphine-treated male and female rats. These results indicate that the decrease in the magnitudes of the spectral changes is related to the decrease in the hydroxylation of steroid hormones. The magnitude of spectral change induced by progesterone or testosterone per unit of P-450 content was decreased in morphine-treated male rats, but not in the females. Since the binding capacity of P-450 with progesterone or testosterone is dependent on the action of androgen, an impairment of the action of androgen by morphine is assumed to be a responsible factor.