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

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Abstract
The metabolism of labeled 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 .times. 10-6 and 4.2 .times. 10-9 to 1 g (substrate amounts between 57.73 and 0.02 nmol); with both concentrations 42-44% of progesterone was metabolized to about 35% monohydroxymonoketonic steroids and 4-6% dihydroxylated C21O2-compounds. In both sets of incubations the following steroids were isolated and identified: 3.alpha.-hydroxy-5.alpha.-pregnan-20-one, 3.beta.-hydroxy-4-pregnen-20-one, 3.alpha.-hydroxy-4-pregnen-20-one, 20.alpha.-hydroxy-4-pregnen-3-one, 5.alpha.-pregnane-3.alpha.,20.alpha.-diol and 4-pregnene-3.alpha.,20.alpha.-diol. The most abundant metabolite formed in these incubations was 3.alpha.-hydroxy-4-pregnen-20-one, which corresponds to about 30% of the total activity recovered. It is the 1st time that the presence of 20.alpha.-hydroxysteroid-oxidoreductase activity is definitely established in this type of tisse. The identification of 3 allylic alcohols as progesterone metabolites in the rat uterus confirms that .DELTA.4-3-hydroxysteroids are important intermediates in the in vitro uterine metabolism of steroids.

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