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Molecular Pharmacology, Vol 4, 109-120, Copyright © 1968 by the American Society for Pharmacology and Experimental Therapeutics

Thyroid Hormone and Activities of Drug-Metabolizing Enzymes and Electron Transport Systems of Rat Liver Microsomes

RYUICHI KATO 1 and ATSUSHI TAKAHASHI 1

1 Department of Pharmacology, National Institute of Hygienic Sciences, Tamagawayoga-machi, Setagaya-ku, Japan

Drug-metabolizing activities of liver microsomes and the activities of microsomal electron transport systems were investigated in male and female rats with altered thyroid states.

The administration of thyroxine decreased the N-demethylation of aminopyrine and hydroxylation of hexobarbital by liver microsomes in male rats. In contrast, the same treatment increased the metabolism of aminopyrine and hexobarbital in female rats. The hydroxylation of aniline and reduction of p-nitrobenzoic acid were increased in both male and female rats.

The administration of thyroxine increased the activity of microsomal NADPH oxidase, NADPH-cytochrome c reductase, and NADPH-neotetrazolium reductase in both male and female rats, but the magnitude of increase was much greater in female rats than in male rats. The content of P-450 was decreased in male rats, but this content was not significantly altered in female rats.

The metabolism of aminopyrine, hexobarbital, aniline, and p-nitrobenzoic acid and the activities of NADPH oxidase, NADPH-cytochrome c reductase, NADPH-neotetrazolium reductase, and NADH oxidase were decreased in the thyroidectomized male and female rats, but the activity of NADH-cytochrome c reductase and cytochrome b5 and the P-450 content were not significantly altered.

The administration of triiodothyronine completely restored all values in the thyroidectomized female rats, but the activities of aminopyrine N-demethylase, hexobarbital hydroxylase, and NADPH-neotetrazolium reductase and P-450 content remained low in the male rats.

The stimulative effect of phenobarbital administration on the microsomal enzymes was observed in the thyroxine-treated rats and thyroidectomized rats as well as in normal rats.

Submitted on June 9, 1967
Revised on September 29, 1967






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