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Journal of Pharmacology And Experimental Therapeutics, Vol. 150, Issue 2, 285-291, 1965
Copyright © 1965 by American Society for Pharmacology and Experimental Therapeutics

SEX DIFFERENCES IN THE EFFECTS OF ABNORMAL PHYSIOLOGICAL STATES ON THE METABOLISM OF DRUGS BY RAT LIVER MICROSOMES

Ryuichi Kato 1 and James R. Gillette 1

1 Laboratory of Chemical Pharmacology, National Heart Institute, National Institutes of Health, Bethesda, Maryland

Although the metabolism of aminopyrine and hexobarbital by liver microsomes of male rats is impaired by adrenalectomy, castration, hypoxia, and by the administration of ACTH, formaldehyde, epinephrine, morphine, alloxan or thyroxine, the metabolism of aniline and zoxazolamine is not appreciably decreased by any of these treatments; in fact, hydroxylation of aniline is enhanced by administration of thyroxine and alloxan. Since there is a marked sex difference in the metabolism of aminopyrine and hexobarbital but virtually no sex difference in the hydroxylation of zoxazolamine and aniline, these findings suggest that the various treatments impair mainly the sex-dependent enzymes in liver microsomes.

In support of this view, the metabolism of aminopyrine, hexobarbital, aniline, and zoxazolamine by liver microsomes of female rats is not significantly impaired by any of the various treatments; in fact, alloxan and thyroxine in female rats enhance the metabolism of aminopyrine, aniline, and zoxazolamine by liver microsomes. Moreover, the impairing effects of alloxan, morphine, and thyroxine on the metabolism of hexobarbital and aminopyrine do not occur in castrated male or female rats, but become evident in castrated rats receiving methyltestosterone.

Accepted on June 10, 1965




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