[Changes in testosterone oxidation in rat liver microsomes after prolonged administration of ethylmorphine]

Ethylmorphine administration to male rats during 3 weeks markedly decreased the cytochrome P-450 content and the rate of oxidation of ethylmorphine, hexobarbital and testosterone in liver microsomes. The decrease of the substrate oxidation rate was correlated with the decrease in the maximal spectral changes induced by the substrate binding to cytochrome P-450. Calculation of the substrate oxidation and binding data per mole of cytochrome P-450 showed that considerable changes were observed in the case of testosterone only. A combined administration of testosterone and ethylmorphine did not prevent the decrease of the substrate oxidation. It was assumed that a prolonged administration of ethylmorphine causes a decline of the form of cytochrome P-450 involved in testosterone metabolism and that testosterone does not directly control the content and activity of microsomal hydroxylases.