Sex steroids and extrahepatic mixed-function oxidase activity

Abstract

The effects of exogenously administered testosterone and estradiol on the cytochrome(s) P-450-linked mixed-function oxidase system of the lungs and kidneys of both intact and castrated male and female Sprague-Dawley rats have been investigated. In general, estrogen increased the levels of renal cytochrome(s) P-450 in both male and female intact and castrated rats but decreased enzyme activity as measured by the deethylations of ethoxycoumarin and ethoxyresorufin. These effects were more pronounced in male rats than in the females. Testosterone had no effect on the levels of renal cytochrome(s) P-450 but basal levels were greater in intact males than in females. In the lungs of intact animals, levels of cytochrome(s) P-450 were higher in females than in males, but remained unaffected by pretreatment with testosterone and estradiol. In castrated animals, estrogen increased the levels of cytochrome(s) P-450 while testosterone decreased them. Estrogen treatment, in both intact and castrated males, enhanced the O-deethylation of ethoxyresorufin, implying greater activity of the cytochrome P 1-450-linked mixed-function oxidase activity of the lung. The possible roles of the extrahepatic mixed-function oxidase activity and sex differences in drug metabolism are discussed.