Androgenic repression of hexobarbitone metabolism and action in Crl:CD-1 (ICR)BR mice.
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.
D000375:Aging; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D002369:Castration; D005260:Female; D006591:Hexobarbital / Q000037:antagonists & inhibitors / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008862:Microsomes, Liver / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012737:Sex Factors; D013739:Testosterone / Q000494:pharmacology
D000728:Androgens; D011506:Proteins; D013739:Testosterone; D006591:Hexobarbital; D006899:Mixed Function Oxygenases; C021352:hexobarbital hydroxylase