Androgenic repression of hexobarbitone metabolism and action in Crl:CD‐1 (ICR)BR mice

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Abstract
Mice of the Crl:CD‐1 (ICR)BR strain exhibit a sexual dimorphism in hexobarbitone metabolism and action. Compared to females, males have a lower Vmax and a higher Km for hepatic microsomal hexobarbitone hydroxylase. In agreement with the enzyme studies, hexobarbitone‐induced sleeping times were greater for males than for females. Results from experiments measuring hexobarbitone metabolism and action in castrate, testosterone and gonadotropin‐treated mice indicate that the sexual differences in drug metabolism and action found in Crl:CD‐1 (ICR)BR mice are due to the normally repressive effects of testicular androgens on the activities of the hepatic mono‐oxygenases. These findings are in dramatic contrast to studies with rats where it has been shown that androgens induce mono‐oxygenases. Furthermore, in the case of the mouse, changes in the activity of hexobarbitone hydroxylase in response to alterations in androgen levels require weeks, while in the rat, androgenic‐induced changes are apparent within a matter of days.

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