Direct effect of androgens on progesterone binding and metabolism in rat testis microsomes

A possible site of action at which androgens may control their own biosynthesis in rat testicular tissue in terms of an intratesticular feedback mechanism is investigated. It is shown that both progesterone (Ks = 0.45 microM) and testosterone (Ks = 14.7 microM) induce spectral changes at microsomal cytochrome P-450; these spectral effects are not additive and therefore both steroids may act on the same species of cytochrome P-450. This hypothesis is supported by the observation of competitive inhibition by testosterone of progesterone binding to solubilized microsomal proteins (Ki = 10.0 microM) and of progesterone conversion to androgens (Ki = 14.3 microM). It is concluded that rat testicular androgen biosynthesis is subject to feedback regulation not only via the pituitary-testicular axis but also by direct action of androgens on microsomal reactions dependent on progesterone-binding cytochrome P-450.