3 alpha hydroxysteroid dehydrogenase

Summary

Gene Symbol: 3 alpha hydroxysteroid dehydrogenase
Description: aldo-keto reductase family 1, member C14
Alias: Akr1c9, 3-alpha-hydroxysteroid dehydrogenase, 3-alpha-HSD, hydroxyprostaglandin dehydrogenase, steroid 3-alpha-dehydrogenase
Species: rat

Top Publications

  1. Pawlowski J, Huizinga M, Penning T. Isolation and partial characterization of a full-length cDNA clone for 3 alpha-hydroxysteroid dehydrogenase: a potential target enzyme for nonsteroidal anti-inflammatory drugs. Agents Actions. 1991;34:289-93 pubmed
    ..cytosol is a monomeric (Mr 34000) NAD(P)+ dependent oxidoreductase which displays 9-, 11- & 15-hydroxyprostaglandin dehydrogenase activity...
  2. Cheng K. Molecular cloning of rat liver 3?-hydroxysteroid dehydrogenase and identification of structurally related proteins from rat lung and kidney. J Steroid Biochem Mol Biol. 1992;43:1083-8 pubmed publisher
  3. Usui E, Okuda K, Kato Y, Noshiro M. Rat hepatic 3 alpha-hydroxysteroid dehydrogenase: expression of cDNA and physiological function in bile acid biosynthetic pathway. J Biochem. 1994;115:230-7 pubmed
    ..abstract truncated at 250 words) ..
  4. Khanna M, Qin K, Cheng K. Distribution of 3 alpha-hydroxysteroid dehydrogenase in rat brain and molecular cloning of multiple cDNAs encoding structurally related proteins in humans. J Steroid Biochem Mol Biol. 1995;53:41-6 pubmed
    ..We are currently investigating the functional relationship between the enzymes encoded by these human cDNAs and 3 alpha-hydroxysteroid dehydrogenase. ..
  5. Heredia V, Cooper W, Kruger R, Jin Y, Penning T. Alanine scanning mutagenesis of the testosterone binding site of rat 3 alpha-hydroxysteroid dehydrogenase demonstrates contact residues influence the rate-determining step. Biochemistry. 2004;43:5832-41 pubmed
    ..and steroid turnover by these enzymes were analyzed using rat 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD, AKR1C9) as the protein model...
  6. Hoog S, Pawlowski J, Alzari P, Penning T, Lewis M. Three-dimensional structure of rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase: a member of the aldo-keto reductase superfamily. Proc Natl Acad Sci U S A. 1994;91:2517-21 pubmed
    ..In the 3 alpha-HSD structure these residues are on the periphery of the barrel and are unlikely to participate in catalysis. ..
  7. Bennett M, Schlegel B, Jez J, Penning T, Lewis M. Structure of 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase complexed with NADP+. Biochemistry. 1996;35:10702-11 pubmed
    ..Knowledge of the position of this water molecule, combined with the stereochemistry of hydride transfer, suggests that the alpha face of a bound steroid will be oriented toward the side of the apolar cleft containing Trp 86. ..
  8. Cooper W, Jin Y, Penning T. Elucidation of a complete kinetic mechanism for a mammalian hydroxysteroid dehydrogenase (HSD) and identification of all enzyme forms on the reaction coordinate: the example of rat liver 3alpha-HSD (AKR1C9). J Biol Chem. 2007;282:33484-93 pubmed
    ..the complete kinetic mechanism of a mammalian HSD using rat 3alpha-HSD of the aldo-keto reductase superfamily (AKR1C9) with the substrate pairs androstane-3,17-dione and NADPH (reduction) and androsterone and NADP(+) (oxidation)...
  9. Patte Mensah C, Penning T, Mensah Nyagan A. Anatomical and cellular localization of neuroactive 5 alpha/3 alpha-reduced steroid-synthesizing enzymes in the spinal cord. J Comp Neurol. 2004;477:286-99 pubmed
    ..These results are the first demonstrating that oligodendrocytes and neurons of the SC possess the key enzymatic complex for synthesizing potent neuroactive steroids that may control spinal sensorimotor processes. ..
  10. Stolz A, Rahimi Kiani M, Ameis D, Chan E, Ronk M, Shively J. Molecular structure of rat hepatic 3 alpha-hydroxysteroid dehydrogenase. A member of the oxidoreductase gene family. J Biol Chem. 1991;266:15253-7 pubmed
    ..The significant homology of 3 alpha-HSD with both prostaglandin F synthetase and aldose reductases suggest a subdivision of monomeric, NADPH reductases within the larger oxidoreductases superfamily. ..

Detail Information

Publications18

  1. Pawlowski J, Huizinga M, Penning T. Isolation and partial characterization of a full-length cDNA clone for 3 alpha-hydroxysteroid dehydrogenase: a potential target enzyme for nonsteroidal anti-inflammatory drugs. Agents Actions. 1991;34:289-93 pubmed
    ..cytosol is a monomeric (Mr 34000) NAD(P)+ dependent oxidoreductase which displays 9-, 11- & 15-hydroxyprostaglandin dehydrogenase activity...
  2. Cheng K. Molecular cloning of rat liver 3?-hydroxysteroid dehydrogenase and identification of structurally related proteins from rat lung and kidney. J Steroid Biochem Mol Biol. 1992;43:1083-8 pubmed publisher
  3. Usui E, Okuda K, Kato Y, Noshiro M. Rat hepatic 3 alpha-hydroxysteroid dehydrogenase: expression of cDNA and physiological function in bile acid biosynthetic pathway. J Biochem. 1994;115:230-7 pubmed
    ..abstract truncated at 250 words) ..
  4. Khanna M, Qin K, Cheng K. Distribution of 3 alpha-hydroxysteroid dehydrogenase in rat brain and molecular cloning of multiple cDNAs encoding structurally related proteins in humans. J Steroid Biochem Mol Biol. 1995;53:41-6 pubmed
    ..We are currently investigating the functional relationship between the enzymes encoded by these human cDNAs and 3 alpha-hydroxysteroid dehydrogenase. ..
  5. Heredia V, Cooper W, Kruger R, Jin Y, Penning T. Alanine scanning mutagenesis of the testosterone binding site of rat 3 alpha-hydroxysteroid dehydrogenase demonstrates contact residues influence the rate-determining step. Biochemistry. 2004;43:5832-41 pubmed
    ..and steroid turnover by these enzymes were analyzed using rat 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD, AKR1C9) as the protein model...
  6. Hoog S, Pawlowski J, Alzari P, Penning T, Lewis M. Three-dimensional structure of rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase: a member of the aldo-keto reductase superfamily. Proc Natl Acad Sci U S A. 1994;91:2517-21 pubmed
    ..In the 3 alpha-HSD structure these residues are on the periphery of the barrel and are unlikely to participate in catalysis. ..
  7. Bennett M, Schlegel B, Jez J, Penning T, Lewis M. Structure of 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase complexed with NADP+. Biochemistry. 1996;35:10702-11 pubmed
    ..Knowledge of the position of this water molecule, combined with the stereochemistry of hydride transfer, suggests that the alpha face of a bound steroid will be oriented toward the side of the apolar cleft containing Trp 86. ..
  8. Cooper W, Jin Y, Penning T. Elucidation of a complete kinetic mechanism for a mammalian hydroxysteroid dehydrogenase (HSD) and identification of all enzyme forms on the reaction coordinate: the example of rat liver 3alpha-HSD (AKR1C9). J Biol Chem. 2007;282:33484-93 pubmed
    ..the complete kinetic mechanism of a mammalian HSD using rat 3alpha-HSD of the aldo-keto reductase superfamily (AKR1C9) with the substrate pairs androstane-3,17-dione and NADPH (reduction) and androsterone and NADP(+) (oxidation)...
  9. Patte Mensah C, Penning T, Mensah Nyagan A. Anatomical and cellular localization of neuroactive 5 alpha/3 alpha-reduced steroid-synthesizing enzymes in the spinal cord. J Comp Neurol. 2004;477:286-99 pubmed
    ..These results are the first demonstrating that oligodendrocytes and neurons of the SC possess the key enzymatic complex for synthesizing potent neuroactive steroids that may control spinal sensorimotor processes. ..
  10. Stolz A, Rahimi Kiani M, Ameis D, Chan E, Ronk M, Shively J. Molecular structure of rat hepatic 3 alpha-hydroxysteroid dehydrogenase. A member of the oxidoreductase gene family. J Biol Chem. 1991;266:15253-7 pubmed
    ..The significant homology of 3 alpha-HSD with both prostaglandin F synthetase and aldose reductases suggest a subdivision of monomeric, NADPH reductases within the larger oxidoreductases superfamily. ..
  11. Del Bello B, Maellaro E, Sugherini L, Santucci A, Comporti M, Casini A. Purification of NADPH-dependent dehydroascorbate reductase from rat liver and its identification with 3 alpha-hydroxysteroid dehydrogenase. Biochem J. 1994;304 ( Pt 2):385-90 pubmed
    ..Internal primary structure data were obtained from CNBr-derived fragments and definitely proved the identity of NADPH-dependent DHAA reductase with 3 alpha-hydroxysteroid dehydrogenase. ..
  12. Penning T, Abrams W, Pawlowski J. Affinity labeling of 3 alpha-hydroxysteroid dehydrogenase with 3 alpha-bromoacetoxyandrosterone and 11 alpha-bromoacetoxyprogesterone. Isolation and sequence of active site peptides containing reactive cysteines; sequence confirmation using nucleotid. J Biol Chem. 1991;266:8826-34 pubmed
    ..By contrast the 11 alpha-bromoacetoxy group in Br11P labeled several reactive cysteines which may be involved in the binding of glucocorticoids and NSAIDs. ..
  13. Pawlowski J, Huizinga M, Penning T. Cloning and sequencing of the cDNA for rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase. J Biol Chem. 1991;266:8820-5 pubmed
    ..It is identical to dihydrodiol dehydrogenase and it can function as a 9-, 11-, and 15-hydroxyprostaglandin dehydrogenase. Its reactions are potently inhibited by the nonsteroidal anti-inflammatory drugs (NSAIDs)...
  14. Guo J, Li L, Zhou S, Su Y, Li X, Sun J, et al. Butylated hydroxyanisole alters rat 5?-reductase and 3?-hydroxysteroid dehydrogenase: Implications for influences of neurosteroidogenesis. Neurosci Lett. 2017;653:132-138 pubmed publisher
    ..In conclusion, butylated hydroxyanisole is a potent inhibitor of SRD5A1 and AKR1C14, thus reducing the formation of active neurosteroids. ..
  15. Lin H, Hung C, Moore M, Penning T. Genomic structure of rat 3alpha-hydroxysteroid/dihydrodiol dehydrogenase (3alpha-HSD/DD, AKR1C9). J Steroid Biochem Mol Biol. 1999;71:29-39 pubmed
    ..It is unknown whether the type 2 and type 3 3alpha-HSD/DD genes represent pseudo-genes or whether they represent genes that are differentially expressed in other rat tissues. ..
  16. Heredia V, Penning T. Dissection of the physiological interconversion of 5alpha-DHT and 3alpha-diol by rat 3alpha-HSD via transient kinetics shows that the chemical step is rate-determining: effect of mutating cofactor and substrate-binding pocket residues on catalysis. Biochemistry. 2004;43:12028-37 pubmed
    ..To identify the rate-determining step in this physiologically important reaction, rat liver 3alpha-HSD (AKR1C9) was used as the protein model for the human homologues in fluorescence stopped-flow transient kinetic and kinetic ..
  17. Cheng K, White P, Qin K. Molecular cloning and expression of rat liver 3 alpha-hydroxysteroid dehydrogenase. Mol Endocrinol. 1991;5:823-8 pubmed
    Complementary DNA clones encoding 3 alpha-hydroxysteroid dehydrogenase (3 alpha HSD) were isolated from a rat liver cDNA lambda gt11 expression library using monoclonal antibodies as probes. The sizes of the cDNA inserts ranged from 1...
  18. Kimoto T, Ishii H, Higo S, Hojo Y, Kawato S. Semicomprehensive analysis of the postnatal age-related changes in the mRNA expression of sex steroidogenic enzymes and sex steroid receptors in the male rat hippocampus. Endocrinology. 2010;151:5795-806 pubmed publisher
    ..These results suggest that the hippocampal sex steroidogenic properties are substantially altered during the postnatal development processes, which might contribute to brain sexual maturation. ..