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Jian Su, Min Lin, Joseph L. Napoli, Complementary Deoxyribonucleic Acid Cloning and Enzymatic Characterization of a Novel 17β/3α-Hydroxysteroid/Retinoid Short Chain Dehydrogenase/Reductase, Endocrinology, Volume 140, Issue 11, 1 November 1999, Pages 5275–5284, https://doi.org/10.1210/endo.140.11.7137
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Abstract
17β-Hydroxysteroid dehydrogenases (17βHSDs) convert androgens and estrogens between their active and inactive forms, whereas retinol dehydrogenases catalyze the conversion between retinol and retinal. Retinol dehydrogenases function in the visual cycle, in the generation of the hormone retinoic acid, and some also act on androgens. Here we report cloning and expression of a complementary DNA that encodes a new mouse liver microsomal member of the short chain dehydrogenase/reductase (SDR) superfamily and its enzymatic characterization, i.e. 17βHSD9. Although 17βHSD9 shares 88% amino acid identity with rat 17βHSD6, its closest homolog, the two differ in substrate specificity. In contrast to other 17βHSD, 17βHSD9 has nearly equivalent activities as a 17βHSD (with estradiol ≃ adiol) and as a 3αHSD (with adiol ≃ androsterone). It also recognizes retinol as substrate and represents in part the NAD+-dependent liver microsomal dehydrogenase that uses unbound retinol, but not retinol complexed with cellular retinol-binding protein. Thus, this enzyme has catalytic properties that overlap with two subgroups of SDR, 17βHSD and retinol dehydrogenases. Inactivation of estrogen and a variety of androgens seems to be its most probable function. Because of its apparent inability to access retinol bound with cellular retinol-binding protein, a function in the pathway of retinoic acid biosynthesis seems less obvious. These data provide additional insight into the enzymology of estrogen, androgen, and retinoid metabolism and illustrate how closely related members of the SDR superfamily can have strikingly different substrate specificities.
