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. 1995 Oct 15;311(Pt 2):437–443. doi: 10.1042/bj3110437

Molecular cloning of a novel widely expressed human 80 kDa 17 beta-hydroxysteroid dehydrogenase IV.

J Adamski 1, T Normand 1, F Leenders 1, D Monté 1, A Begue 1, D Stéhelin 1, P W Jungblut 1, Y de Launoit 1
PMCID: PMC1136019  PMID: 7487879

Abstract

Reactions of oestrogens and androgens at position C-17 are catalysed by 17 beta-hydroxysteroid dehydrogenases (17 beta-HSDs). Cloning of the cDNA of a novel human 17 beta-HSD IV and expression of its mRNA are described. A probe derived from the recently discovered porcine 17 beta-oestradiol dehydrogenase (17 beta-EDH) was used to isolate a 2.6 kb human cDNA encoding a continuous protein of 736 amino acids of high (84%) similarity to the porcine 17 beta-EDH. The calculated molecular mass of the human enzyme is 79,595 Da. Other sequence similarities shared by the two enzymes are: an N-terminal sequence which is similar to that of members of the short-chain alcohol dehydrogenase family; amino acids 343-607 which are similar to the C-terminal domains of a trifunctional Candida tropicalis enzyme and the FOX2 gene product of Saccharomyces cerevisiae; amino acids 596-736 which are similar to human sterol carrier protein 2. The previously cloned human 17 beta-HSD I, II and III are less than 25% identical with 17 beta-HSD IV. mRNA for HSD IV is a single species of 3.0 kb, present in many tissues with highest concentrations in liver, heart, prostate and testes. When over-expressed in mammalian cells, the human 17 beta-HSD IV enzyme displays a specific unidirectional oxidative 17 beta-HSD activity.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams E. F., Coldham N. G., James V. H. Steroidal regulation of oestradiol-17 beta dehydrogenase activity of the human breast cancer cell line MCF-7. J Endocrinol. 1988 Jul;118(1):149–154. doi: 10.1677/joe.0.1180149. [DOI] [PubMed] [Google Scholar]
  2. Adamski J., Husen B., Marks F., Jungblut P. W. Purification and properties of oestradiol 17 beta-dehydrogenase extracted from cytoplasmic vesicles of porcine endometrial cells. Biochem J. 1992 Dec 1;288(Pt 2):375–381. doi: 10.1042/bj2880375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Adamski J., Husen B., Marks F., Jungblut P. W. The 17 beta-oestradiol dehydrogenase of pig endometrial cells is localized in specialized vesicles. Biochem J. 1993 Mar 15;290(Pt 3):777–782. doi: 10.1042/bj2900777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Adamski J., Sierralta W. D., Jungblut P. W. Assignment of estradiol-17 beta dehydrogenase and of estrone reductase to cytoplasmic structures of porcine endometrium cells. Acta Endocrinol (Copenh) 1989 Aug;121(2):161–167. doi: 10.1530/acta.0.1210161. [DOI] [PubMed] [Google Scholar]
  5. Baker M. E. A common ancestor for Candida tropicalis and dehydrogenases that synthesize antibiotics and steroids. FASEB J. 1990 Sep;4(12):3028–3032. doi: 10.1096/fasebj.4.12.2394320. [DOI] [PubMed] [Google Scholar]
  6. Blomquist C. H., Lindemann N. J., Hakanson E. Y. 17 beta-hydroxysteroid and 20 alpha-hydroxysteroid dehydrogenase activities of human placental microsomes: kinetic evidence for two enzymes differing in substrate specificity. Arch Biochem Biophys. 1985 May 15;239(1):206–215. doi: 10.1016/0003-9861(85)90828-8. [DOI] [PubMed] [Google Scholar]
  7. Carsol J. L., Martin P. M., de Launoit Y. Characterization of 17 beta-hydroxysteroid dehydrogenase activity and mRNA abundance in human meningioma tumors. Neuroendocrinology. 1994 Oct;60(4):445–451. doi: 10.1159/000126779. [DOI] [PubMed] [Google Scholar]
  8. Chen Z., Jiang J. C., Lin Z. G., Lee W. R., Baker M. E., Chang S. H. Site-specific mutagenesis of Drosophila alcohol dehydrogenase: evidence for involvement of tyrosine-152 and lysine-156 in catalysis. Biochemistry. 1993 Apr 6;32(13):3342–3346. doi: 10.1021/bi00064a017. [DOI] [PubMed] [Google Scholar]
  9. Dumont M., Luu-The V., de Launoit Y., Labrie F. Expression of human 17 beta-hydroxysteroid dehydrogenase in mammalian cells. J Steroid Biochem Mol Biol. 1992 Mar;41(3-8):605–608. doi: 10.1016/0960-0760(92)90391-u. [DOI] [PubMed] [Google Scholar]
  10. Engel L. L., Groman E. V. Human placental 17beta-estradiol dehydrogenase: characterization and structural studies. Recent Prog Horm Res. 1974;30(0):139–169. doi: 10.1016/b978-0-12-571130-2.50008-0. [DOI] [PubMed] [Google Scholar]
  11. Entenmann A. H., Sierralta W., Jungblut P. W. Studies on the involvement of lysosomes in estrogen action, III. The dehydrogenation of estradiol to estrone by porcine endometrial lysosomes. Hoppe Seylers Z Physiol Chem. 1980;361(6):959–968. doi: 10.1515/bchm2.1980.361.1.959. [DOI] [PubMed] [Google Scholar]
  12. Gast M. J., Sims H. F., Murdock G. L., Gast P. M., Strauss A. W. Isolation and sequencing of a complementary deoxyribonucleic acid clone encoding human placental 17 beta-estradiol dehydrogenase: identification of the putative cofactor binding site. Am J Obstet Gynecol. 1989 Dec;161(6 Pt 1):1726–1731. doi: 10.1016/0002-9378(89)90958-7. [DOI] [PubMed] [Google Scholar]
  13. Geissler W. M., Davis D. L., Wu L., Bradshaw K. D., Patel S., Mendonca B. B., Elliston K. O., Wilson J. D., Russell D. W., Andersson S. Male pseudohermaphroditism caused by mutations of testicular 17 beta-hydroxysteroid dehydrogenase 3. Nat Genet. 1994 May;7(1):34–39. doi: 10.1038/ng0594-34. [DOI] [PubMed] [Google Scholar]
  14. Gompel A., Malet C., Spritzer P., Lalardrie J. P., Kuttenn F., Mauvais-Jarvis P. Progestin effect on cell proliferation and 17 beta-hydroxysteroid dehydrogenase activity in normal human breast cells in culture. J Clin Endocrinol Metab. 1986 Nov;63(5):1174–1180. doi: 10.1210/jcem-63-5-1174. [DOI] [PubMed] [Google Scholar]
  15. Hiltunen J. K., Wenzel B., Beyer A., Erdmann R., Fosså A., Kunau W. H. Peroxisomal multifunctional beta-oxidation protein of Saccharomyces cerevisiae. Molecular analysis of the fox2 gene and gene product. J Biol Chem. 1992 Apr 5;267(10):6646–6653. [PubMed] [Google Scholar]
  16. Husen B., Adamski J., Szendro P. I., Jungblut P. W. Alterations in the subcellular distribution of 17 beta-estradiol dehydrogenase in porcine endometrial cells over the course of the estrous cycle. Cell Tissue Res. 1994 Nov;278(2):227–233. doi: 10.1007/BF00414164. [DOI] [PubMed] [Google Scholar]
  17. Kozak M. Structural features in eukaryotic mRNAs that modulate the initiation of translation. J Biol Chem. 1991 Oct 25;266(30):19867–19870. [PubMed] [Google Scholar]
  18. LANGER L. J., ENGEL L. L. Human placental estradiol-17 beta dehydrogenase. I. Concentration, characterization and assay. J Biol Chem. 1958 Sep;233(3):583–588. [PubMed] [Google Scholar]
  19. Leenders F., Adamski J., Husen B., Thole H. H., Jungblut P. W. Molecular cloning and amino acid sequence of the porcine 17 beta-estradiol dehydrogenase. Eur J Biochem. 1994 May 15;222(1):221–227. doi: 10.1111/j.1432-1033.1994.tb18860.x. [DOI] [PubMed] [Google Scholar]
  20. Leenders F., Husen B., Thole H. H., Adamski J. The sequence of porcine 80 kDa 17 beta-estradiol dehydrogenase reveals similarities to the short chain alcohol dehydrogenase family, to actin binding motifs and to sterol carrier protein 2. Mol Cell Endocrinol. 1994 Sep;104(2):127–131. doi: 10.1016/0303-7207(94)90114-7. [DOI] [PubMed] [Google Scholar]
  21. Lin S. X., Yang F., Jin J. Z., Breton R., Zhu D. W., Luu-The V., Labrie F. Subunit identity of the dimeric 17 beta-hydroxysteroid dehydrogenase from human placenta. J Biol Chem. 1992 Aug 15;267(23):16182–16187. [PubMed] [Google Scholar]
  22. Lipman D. J., Pearson W. R. Rapid and sensitive protein similarity searches. Science. 1985 Mar 22;227(4693):1435–1441. doi: 10.1126/science.2983426. [DOI] [PubMed] [Google Scholar]
  23. Luu The V., Labrie C., Zhao H. F., Couët J., Lachance Y., Simard J., Leblanc G., Côté J., Bérubé D., Gagné R. Characterization of cDNAs for human estradiol 17 beta-dehydrogenase and assignment of the gene to chromosome 17: evidence of two mRNA species with distinct 5'-termini in human placenta. Mol Endocrinol. 1989 Aug;3(8):1301–1309. doi: 10.1210/mend-3-8-1301. [DOI] [PubMed] [Google Scholar]
  24. Luu-The V., Labrie C., Simard J., Lachance Y., Zhao H. F., Couët J., Leblanc G., Labrie F. Structure of two in tandem human 17 beta-hydroxysteroid dehydrogenase genes. Mol Endocrinol. 1990 Feb;4(2):268–275. doi: 10.1210/mend-4-2-268. [DOI] [PubMed] [Google Scholar]
  25. Martel C., Rhéaume E., Takahashi M., Trudel C., Couët J., Luu-The V., Simard J., Labrie F. Distribution of 17 beta-hydroxysteroid dehydrogenase gene expression and activity in rat and human tissues. J Steroid Biochem Mol Biol. 1992 Mar;41(3-8):597–603. doi: 10.1016/0960-0760(92)90390-5. [DOI] [PubMed] [Google Scholar]
  26. Monté D., Baert J. L., Defossez P. A., de Launoit Y., Stéhelin D. Molecular cloning and characterization of human ERM, a new member of the Ets family closely related to mouse PEA3 and ER81 transcription factors. Oncogene. 1994 May;9(5):1397–1406. [PubMed] [Google Scholar]
  27. Nuttley W. M., Aitchison J. D., Rachubinski R. A. cDNA cloning and primary structure determination of the peroxisomal trifunctional enzyme hydratase-dehydrogenase-epimerase from the yeast Candida tropicalis pK233. Gene. 1988 Sep 30;69(2):171–180. doi: 10.1016/0378-1119(88)90428-3. [DOI] [PubMed] [Google Scholar]
  28. Peltoketo H., Isomaa V., Mäentausta O., Vihko R. Complete amino acid sequence of human placental 17 beta-hydroxysteroid dehydrogenase deduced from cDNA. FEBS Lett. 1988 Oct 24;239(1):73–77. doi: 10.1016/0014-5793(88)80548-9. [DOI] [PubMed] [Google Scholar]
  29. Persson B., Krook M., Jörnvall H. Characteristics of short-chain alcohol dehydrogenases and related enzymes. Eur J Biochem. 1991 Sep 1;200(2):537–543. doi: 10.1111/j.1432-1033.1991.tb16215.x. [DOI] [PubMed] [Google Scholar]
  30. Poutanen M., Isomaa V., Kainulainen K., Vihko R. Progestin induction of 17 beta-hydroxysteroid dehydrogenase enzyme protein in the T-47D human breast-cancer cell line. Int J Cancer. 1990 Nov 15;46(5):897–901. doi: 10.1002/ijc.2910460524. [DOI] [PubMed] [Google Scholar]
  31. Poutanen M., Miettinen M., Vihko R. Differential estrogen substrate specificities for transiently expressed human placental 17 beta-hydroxysteroid dehydrogenase and an endogenous enzyme expressed in cultured COS-m6 cells. Endocrinology. 1993 Dec;133(6):2639–2644. doi: 10.1210/endo.133.6.8243287. [DOI] [PubMed] [Google Scholar]
  32. Reed M. J. Oestradiol-17 beta hydroxysteroid dehydrogenase: its family and function. J Endocrinol. 1991 May;129(2):163–165. doi: 10.1677/joe.0.1290163. [DOI] [PubMed] [Google Scholar]
  33. Seedorf U., Assmann G. Cloning, expression, and nucleotide sequence of rat liver sterol carrier protein 2 cDNAs. J Biol Chem. 1991 Jan 5;266(1):630–636. [PubMed] [Google Scholar]
  34. Seedorf U., Scheek S., Engel T., Steif C., Hinz H. J., Assmann G. Structure-activity studies of human sterol carrier protein 2. J Biol Chem. 1994 Jan 28;269(4):2613–2618. [PubMed] [Google Scholar]
  35. Tremblay Y., Beaudoin C. Regulation of 3 beta-hydroxysteroid dehydrogenase and 17 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid levels by cyclic adenosine 3',5'-monophosphate and phorbol myristate acetate in human choriocarcinoma cells. Mol Endocrinol. 1993 Mar;7(3):355–364. doi: 10.1210/mend.7.3.8387158. [DOI] [PubMed] [Google Scholar]
  36. Tseng L., Gurpide E. Estradiol and 20alpha-dihydroprogesterone dehydrogenase activities in human endometrium during the menstrual cycle. Endocrinology. 1974 Feb;94(2):419–423. doi: 10.1210/endo-94-2-419. [DOI] [PubMed] [Google Scholar]
  37. Wickens M. How the messenger got its tail: addition of poly(A) in the nucleus. Trends Biochem Sci. 1990 Jul;15(7):277–281. doi: 10.1016/0968-0004(90)90054-f. [DOI] [PubMed] [Google Scholar]
  38. de Hoop M. J., Ab G. Import of proteins into peroxisomes and other microbodies. Biochem J. 1992 Sep 15;286(Pt 3):657–669. doi: 10.1042/bj2860657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. de Launoit Y., Zhao H. F., Bélanger A., Labrie F., Simard J. Expression of liver-specific member of the 3 beta-hydroxysteroid dehydrogenase family, an isoform possessing an almost exclusive 3-ketosteroid reductase activity. J Biol Chem. 1992 Mar 5;267(7):4513–4517. [PubMed] [Google Scholar]

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