17β-Hydroxysteroid dehydrogenase type 9 and other short-chain dehydrogenases/reductases that catalyze retinoid, 17β- and 3α-hydroxysteroid metabolism

[摘要] Subgroups of related short-chain dehydrogenase/reductase (SDR) family members serve as retinoid/androgen/estrogen metabolizing enzymes. These include retinol dehydrogenases (RoDHs) 1-3, cis-retinol/androgen dehydrogenase 1 and 2 (CRAD), retSDRs1-4, 9/11-cis-retinol dehydrogenase, and 17 beta -hydroxysteroid dehydrogenase (17 beta -HSD) types 6 and 9. Interaction with cellular retinol-binding protein (CRBP), the major physiological form of retinol, led to the identification and cDNA cloning of RoDHI. Probes for RoDHI contributed to cDNA cloning many of the others. Some of these SDRs show specificity with all-trans-retinol (RoDH, retSDR, 17 beta -HSD6 and 9) and others with 9 and/or 11-cis-retinol (CRAD, 9/11-cis-retinol dehydrogenase). Many have 3 alpha -HSD activities with 3 alpha -androstandiol as the most efficiently used substrate, followed by androsterone. In addition to 3 alpha -HSD activity. CRAD2 shows relatively weak 17 beta -HSD activity with testosterone. fiat 17 beta -HSD6 and mouse 17 beta -HSD9, which are not interspecies homologs, have efficient 17 beta -HSD activities. 17 beta -HSD6 has similar to 50% greater 17 beta -HSD activity with estradiol than with 3 alpha -androstandiol. With 3 alpha -androstandiol, 17 beta -HSD9 operates equally efficiently as a 17 beta -HSD or a 3 alpha -HSD. The multi-substrate nature of these SDRs allows for retinoid/steroid interactions. The ability of some these SDRs to access retinol bound with CRBP provides specificity in retinoid metabolism and allows retinoic acid biosynthesis and retinol esterification to continue, as CRBP protects retinol from the general cellular milieu. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

[发布日期] 2001-01-22

[效力级别]  Proceedings Paper

[关键词] 3 alpha-androstanediol;cellular retinol-binding protein;CRAD;estradiol;17 beta-HSD9;retinol;retinol dehydrogenase