Modulation of Hepatic Level of Microsomal Testosterone 7α-Hydroxylase, P-450a (P450IIA), by Thyroid Hormone and Growth Hormone in Rat Liver1

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Abstract
The effects of thyroid hormone and growth hormone on microsomal testosterone 7α-hydroxylase, P-450a, were studied to understand the interaction of these hormonemediated regulations in rats. In Western blots using anti-P-460a IgG, 1.7-fold higher content of P-450a was observed in livers of female than male adult rats, while no appreciable sex-related difference was detected in prepubertal rats and rats of 24 months of age. Treatment with n-propyl-2-thiouracil or thyroidectomy of male rats increased by 2-fold the hepatic content of P-450a, but neither regimen had a significant effect on the content in female rats. Levels of P-450a in both sexes of thyroidectomized rats were decreased by the supplementation of triiodothyronine (T3, 50 μg per kg, i.p. for 7 days) to levels similar to that observed in normal male rats. Hypophysectomy also caused an increase in microsomal P-450a content in male rats. Continuous infusion of human growth hormone, which mimicked the female secretion, further significantly increased the content in hypophysectomized rats to a level similar to that observed in normal female rats. In contrast, hepatic level of P-460a in hypophysectomized male and female rats was reduced by intermittent injection, which mimicked the male secretion. Clear suppression on the level of hepatic P-450a was also observed by the treatment of hypophysectomized rats with 5 or 50 μg/kg of T3 and of hGH-infused hypophysectomized rat with 50 μg/kg of T3. These results suggest that the dual, stimulatory and suppressive, actions of growth hormone on liver P-450a level, which were reproduced, respectively, by the administration schedules designed to mimic female- and male-type secretions, may be responsible for the female dominant expression in livers of adult rats. The present data also indicate that T3 acts at least in part directly on the liver, but not through the hypothalamus-pituitary system, to suppress liver P-450a.

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