<i>In Vitro</i>Metabolism of Progesterone and 20α-Hydroxypregn-4-en-3-one by Tissues of the Female Rat

Abstract

In vitro incubation of progesterone with preparations of muscle and adipose tissue from female rats resulted in the formation of 20α-hydroxypregn-4-en-3-one. Comparison of the 20α-hydroxysteroid dehydrogenase activity of rat ovarian tissue with activities of those enzymes catalyzing reduction of ring A demonstrated a large disparity in favor of side chain reduction. Absence of 3-keto-5α-pregnane intermediates from incubations of ovarian tissue suggested that the rate of ring A reduction was limited by the activity of the Δ4-5α-reductase. Activity of the 20αhydroxysteroid dehydrogenase in ovary contrasted with that in kidney, where it seemed to be only a fraction of the ring A reducing systems. Kidney slices predominantly reduced both progesterone and 20α-hydroxypregn-4-en-3-one to mixtures of their corresponding 3- keto-5α-pregnane and 3α-hydroxy-5α-pregnane derivatives. 3α- and 20α-Hydroxysteroid dehydrogenase activities disappeared following homogenization and were not restored by TPNH addition. Progesterone and 20α-hydroxypregn-4-en-3-one were reduced only in ring A by rat uterine tissue. Activities of 3α-hydroxysteroid dehydrogenase and Δ4- 5α-reductase were most pronounced in uterine segments obtained during estrus and were least pronounced during pseudopregnancy.