Effects of thyroid hormone on the hydroxylation of progesterone in liver microsomes of male and female rats.

Abstract

Progesterone hydroxylation activity of liver microsomes was investigated in male and female rats under altered states of thyroid function. Treatment with thyroxine markedly decreased the activity of progesterone hydroxylation by liver microsomes in male rats, but did not significantly alter the activity in female rats. In contrast, the conversion of progesterone to Δ4-reduced metabolites was increased by treatment of male rats with thyroxine. Thyroidectomy also markedly decreased the progesterone hydroxylating activity in male rats, but did not decrease in female rats. The content of P-450 per microsomal protein and the magnitude of progesterone-induced spectral change per microsomal protein and per P-450 were decreased in thyroxinetreated male rats, but similar changes were not observed in thyroidectomized male rats. From these results it is conceivale that the progesterone hydroxylating activity may be reduced through the decrease in the content of P-450 and the substrate interaction with P-450 in liver microsomes from thyroxine-treated male rats, whereas in those from thyroidectomized rats, the hydroxylating activity may be reduced through the decrease in the reduction of P-450 binding to the substrate. These results indicated that the effects of thyroxine treatment and thyroidectomy on the progesterone hydroxylating activity in liver microsomes of male and female rats were similar to those on the activities of aminopyrine N-demethylation and hexobarbital hydroxylation which are regulated by androgen. On the basis of these results, mechanism(s) of decrease in the progesterone hydroxylating activity in thyroxine-treated and male rats is discussed.