Regulatory effects of 5 beta-reduced steroids.

The first section of this publication summarizes early work according to which 5 beta-pregnanedione is an important metabolite of progesterone in the early stages of the chick embryo's adrenal steroidogenesis, then decreasing gradually as corticosteroidogenesis increases. In the second section a model is described in which adrenal 3 beta-ol hydroxylase-isomerase of the 17-day-old chicken is suppressed pharmacologically, this suppression being correlated with that of the synthesis of aminoevulinic acid (ALA), the first and rate-limiting step of the heme pathway. 5 beta-Pregnanedione (10(-7)-10(-6) M) restored ALA synthesis in this inhibited model to normal values. The effect of 5 beta-pregnanedione was specific since other steroids tested: progesterone; 5 alpha-pregnanedione; corticosterone or estradiol, did not stimulate ALA. Since heme formation by steroidogenic glands contributes to the synthesis of cytochrome P450 rather than hemoglobin, 5 beta-pregnanedione was also assayed as a stimulator of this enzyme system and was found to increase cytochrome P450 in adrenals and testes but not in the liver. In view of these results a hypothesis is advanced according to which 5 beta-reduced progestagens and androgens stimulate cytochrome P450 formation, i.e. the synthesis of progesterone and higher hydroxylated steroids, by steroidogenic glands in the event of an excessive precursor reduction.