Influence of an 18-hydroxyl group on the interaction of oestrogens and hydroxysteroid oxidoreductases

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Abstract
1. Partially purified 17β-hydroxy steroid–NAD+ oxidoreductases, prepared from Pseudomonas testosteroni (EC 1.1.1.51), human term placenta (EC 1.1.1.62) and the cytoplasmic fraction of rat liver (EC 1.1.1.–) were tested for their ability to catalyse the oxidoreduction of 18-hydroxyoestradiol-17β and 18-hydroxyoestrone. The products of incubation were identified by chromatographic procedures and by mass spectrometry. 2. The Pseudomonas enzyme catalysed both the oxidation of 18-hydroxyoestradiol-17β and the reduction of 18-hydroxyoestrone; in contrast, the placental and rat liver enzymes only catalysed the reduction of 18-hydroxyoestrone. 3. These results were confirmed, by using a spectrophotometric assay; equimolar quantities of oestradiol-17β and 18-hydroxyoestradiol-17β were oxidized at approximately the same rate by the microbial enzyme. 4. These findings suggest that 18-hydroxyoestradiol-17β may be a normal oestrogen metabolite. 5. The differences in ability of the mammalian and microbial enzymes to metabolize 18-hydroxylated oestrogens is explained on the basis of recognition sites with different geometrical dimensions, characteristic of the placental (Descomps & Crastes de Paulet, 1969) and the microbial steroid enzymes (Fosset & Crastes de Paulet, 1967).