DOSE-DEPENDENT ACTIONS OF THYROXINE ON HEPATIC DRUG-METABOLISM IN MALE AND FEMALE RATS

Studies were carried out to compare the effects of various doses of thyroxine (T4) on hepatic drug metabolism in male and female rats and to evaluate the role of the pituitary gland in the modulation of T4 action. Administration of small amounts of T4 (2.5 to 5 μg/100g body wt/day) to hypophysectomized rats of either sex increased hepatic ethylmorphine demethylase, benzo(a)pyrene hydroxylase and aniline hydroxylase activities. Larger amounts of T4 (12.5 to 50 μg) reversed the stimulatory effects of the smaller doses. T4 treatment produced dose-dependent decreases in hepatic cytochrome P-450 content and increases in NADPH-cytochrome c reductase activity in hypophysectomized rats of both sexes. Qualitatively similar effects were produced by T4 administration to thyroidectomized male and female rats. However, larger doses of T4 were required for maximum stimulation of drug metabolism in thyroidectomized than in hypophysectomized animals. The results indicate that physiological amounts of T4 Uniformly stimulate hepatic drug metabolism in both male and female rats. Supraphysiological amounts, however, inhibit metabolism of some substrates and produce sex differences in T4 actions. The effects of T4 are demonstrable in the absence of the pituitary gland but pituitary-dependent factors appear to modulate the magnitude of the response to T4. © 1978.