Neonatal Effect of Clomiphene and op´-DDT on Hepatic Oxidative Metabolism of Male Rats

Abstract

The hepatic oxidative metabolism of dehydroepiandrosterone (DHA) and aminopyrine has been investigated in adult rats of both sexes treated neonatally with either clomiphene citrate (100 µg on day 3) or op’-DDT (1 mg daily on days 2–3). The rates of 16α-, 7α- and 7β-hydroxylase activities of DHA and the N-demethylase activities of aminopyrine in hepatic microsomes of normal males were significantly (p < 0.05) higher than those of females. Treatment with clomiphene citrate reduced significantly (p < 0.05) the 16α-hydroxylase activities of males and appeared to suppress the 7α-hydroylase and N-demethylase activities to a lesser extent. Neonatal op’-DDT also reduced these hepatic oxidative activities. Neither treatment affected the 7β-hydroxylase activities. On the other hand, no significant differences in these activities were observed between the control and the treated females, all of which had persistent vaginal estrus. Therefore, it appears that treatment of male neonates with these weak estrogenic compounds antagonizes the androgen-mediated expression of the DHA-16α-hydroxylase activity in liver.

Effect of Clomiphene Citrate on Testicular Steroid Metabolism in Man

“…A direct action of clomiphene citrate upon the aromatizing enzymes is also possible (Aakvaag & Eik-Nes 1969;Smith 8c Day 1963;Hagerinan et al 1969). Furthermore, clomiphene citrate inhibits rat liver 1 Gu-hydroxylase activity (Tabei & Le Roy Heinrichs 1976). Consequently decreased oestradiol synthesis would result in increased levels of oestrone and oestradiol-liB in the human.…”