METABOLISM OF PROGESTERONE IN UTERINE TISSUE OF NON-PREGNANT RATS IN VITRO

Abstract

ABSTRACT The metabolism of labelled progesterone was studied in vitro in uterine tissue of non-pregnant rats with particular emphasis on the influence of substrate concentration. Neither a qualitative nor quantitative difference was found for a steroid tissue ratio between 15 × 10−6 and 4.2 × 10−9 to 1 g (substrate amounts between 57.73 and 0.02 nmol); with both concentrations 42 to 44 per cent of progesterone was metabolized to about 35 per cent monohydroxymonoketonic steroids and 4–6 per cent dihydroxylated C21O2-compounds. In both sets of incubations we have isolated and identified the following steroids: 3α-hydroxy-5α-pregnan-20-one, 3β-hydroxy-4-pregnen-20-one, 3α-hydroxy-4-pregnen-20-one, 20α-hydroxy-4-pregnen-3-one, 5α-pregnane-3α,20α-diol and 4-pregnene-3α,20α-diol. The most abundant metabolite formed in these incubations was 3α-hydroxy-4-pregnen-20-one -which corresponds to about 30 per cent of the total activity recovered. It is the first time that the presence of 20α-hydroxysteroid-oxidoreductase activity is definitely established in this type of tissue. The identification of three allylic alcohols as progesterone metabolites in the rat uterus confirms that Δ4-3-hydroxysteroids are important intermediates in the in vitro uterine metabolism of steroids.