Skip to main content
Log in

17β‐hydroxysteroid dehydrogenases in normal human mammary epithelial cells and breast tissue

  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

17β‐hydroxysteroid dehydrogenase activity represents a group of several isoenzymes (17HSDs) that catalyze the interconversion between highly active 17β‐hydroxy‐ and low activity 17‐ketosteroids and thereby regulate the biological activity of sex steroids. The present study was carried out to characterize the expression of 17HSD isoenzymes in human mammary epithelial cells and breast tissue. In normal breast tissues 17HSD types 1 and 2 mRNAs were both evenly expressed in glandular epithelium. In two human mammary epithelial cell lines, mRNAs for 17HSD types 1, 2 and 4 were detected. In enzyme activity measurements only oxidative 17HSD activity, corresponding to either type 2 or type 4 enzyme, was present. The role of 17HSD type 4 in estrogen metabolism was further investigated, using several cell lines originating from various tissues. No correlation between the presence of 17HSD type 4 mRNA and 17HSD activity in different cultured cell lines was detected. Instead, oxidative 17HSD activity appeared in cell lines where 17HSD type 2 was expressed and reductive 17HSD activity was present in cells expressing 17HSD type 1. These data strongly suggest that in mammary epithelial cell lines the oxidative activity is due to type 2 17HSD and that oxidation of 17β‐hydroxysteroids is not the primary activity of the 17HSD type 4 enzyme.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Cullen KJ, Lippman ME: Estrogen regulation of protein synthesis and cell growth in human breast cancer. Vitam Horm 45: 127–158, 1989

    Google Scholar 

  2. Vihko R, Apter D: Endogenous steroids in the pathophysiology of breast cancer. CRC Crit Rev Oncol/Hematol 9: 1–16, 1989

    Google Scholar 

  3. Labrie F: At the cutting edge: intracrinology. Mol Cell Endocrinol 78: C113–C118, 1991

    Google Scholar 

  4. Stewart PM, Sheppard MC: Novel aspects of hormone action: intracellular ligand supply and its control by series of tissue specific enzymes. Mol Cell Endocrinol 83: C13–C18, 1992

    Google Scholar 

  5. Peltoketo H, Isomaa V, Mäentausta O, Vihko R: Complete amino acid sequence of human placental 17 b-hydroxysteroid dehydrogenase deduced from cDNA. FEBS Lett 239: 73–77, 1988

    Google Scholar 

  6. Wu L, Einstein M, Geissler WM, Chan HK, Elliston KO, Andersson S: Expression cloning and characterization of human17 b-hydroxysteroid dehydrogenase type 2, a microsomal enzyme possessing 20a-hydroxysteroid dehydrogenase activity. J Biol Chem 268: 12964–12969, 1993

    Google Scholar 

  7. Geissler WM, Davis DL, Wu L, Bradshaw KD, Patel S, Mendonca BB, Elliston KO, Wilson JD, Russel DW, Andersson S: Male pseudohermaphroditism caused by mutations of testicular 17 b-hydroxysteroid dehydrogenase 3. Nature Genet 7: 34–39, 1994

    Google Scholar 

  8. Adamski J, Normand T, Leenders F, Monté D, Begue A, Stéhelin D, Jungblut PW, de Launoit Y: Molecular cloning of a novel widely expressed human 80 kDa 17b-hydroxysteroid dehydrogenase IV. Biochem J 311: 437–443, 1995

    Google Scholar 

  9. Ghersevich SA, Poutanen MH, Martikainen HK, Vihko RK: Expression of 17b hydroxysteroid dehydrogenase in human granulosa cells: correlation with follicular size, cytochrome P450 aromatase activity and oestradiol production. J Endocrinol 143: 139–150, 1994

    Google Scholar 

  10. Miettinen MM, Mustonen MVJ, Poutanen MH, Isomaa VV, Vihko RK: Human 17b-hydroxysteroid dehydrogenase type 1 and type 2 isoenzymes have opposite activities in cultured cells and characteristic cell-and tissue-specific expression. Biochem J 314: 839–845, 1996

    Google Scholar 

  11. Adamski J, Husen B, Marks F, Jungblut PW: Purification and properties of oestradiol 17b-dehydrogenase extracted ftom cytoplasmic vesicles of porcine endometrial cells. Biochem J 288: 375–381, 1992

    Google Scholar 

  12. Casey ML, MacDonald PC, Andersson S: 17b-hydroxysteroid dehydrogenase type 2: chromosomal assignment and progestin regulation of gene expression in human endometrium. J Clin Invest 94: 2135–2141, 1994

    Google Scholar 

  13. Elo JP, Akinola LA, Poutanen M, Vihko P, KylIönen AP, Lukkarinen O, Vihko R: Characterization of 17b-hydroxysteroid dehydrogenase isoenzyme expression in benign and malignant human prostate. Int J Cancer 66: 37–41 1996

    Google Scholar 

  14. Dieuaide-Noubhani M, Novikov D, Baumgart E, Vanhooren JCT, Fransen M, Goethals M, Vandekerckhove J, Van Veldhoven PP, Mannaerts GP: Further characterization of the peroxisomal 3-hydroxyacyl-CoA dehydrogenases from rat liver. Relationship between the different dehydrogenases and evidence that fatty acids and the C27 bile acids diand tri-hydroxycoprostanic acids are metabolized by separate multifunctional proteins. Eur J Biochem 240: 660–666, 1996

    Google Scholar 

  15. Qin YM, Poutanen MH, Helander HM, Kvist AP, Siivari KM, Schmitz W, Conzelman E, Hellman U, Hiltunen K: Peroxisomal multifunctional enzyme of b-oxidation metabolizing D-3-hydroxyacyl-CoA esters in rat liver: molecular cloning, expression and characterization. Biochem J 321: 21–28, 1997

    Google Scholar 

  16. Stampfer MR, Bartley JC: Human mammary epithelial cells in culture: Differentiation and transformation. In: Lippmann ME, Dickson RB (eds) Breast Cancer, Cellular and Molecular Biology. Kluwer Academic Publishers, Boston, 1988, pp 1–24

    Google Scholar 

  17. Stampfer MR, Yaswen P: Culture systems for study of human epithelial cell proliferation, differentiation and transformation. Cancer Surveys 18: 7–33, 1993

    Google Scholar 

  18. Normand T, Husen B, Leenders F, Pelczar H, Baert JL, Begue A, Flourens AC, Adamski J, de Launoit Y: Molecular characterization of mouse 17b-hydroxysteroid dehydrogenase IV. J Steroid Biochem Mol Biol 55: 541–548, 1995

    Google Scholar 

  19. Cox KH, De Leon DV, Angerer LM, Angerer RC: Detection of mRNAs in sea urchin embryos by in situ hybridization using asymmetric RNA probes. Dev Biol 101: 485–502, 1984

    Google Scholar 

  20. Mustonen M, Poutanen M, Chotteau-Lelievre A, de Launoit Y, Isomaa V, Vainio S, Vihko R, Vihko P: Ontogeny of 17b-hydroxysteroid dehydrogenase type 2 mRNA expression in the developing mouse placenta and fetus. Mol Cell Endocrinol 134: 33–44, 1997

    Google Scholar 

  21. McNeill JM, Reed MJ, Beranek PA, Newton CJ, Ghilchik MW, James VHT: A comparison of the in vivo uptake and metabolism of [3H] oestrone and [3H] oestradiol by normal breast and breast tumor tissues in postmenopausal women. Int J Cancer 15: 193–196, 1986

    Google Scholar 

  22. van Landeghem AAJ, Poortman J, Nabruus M, Thijssen JHH: Endogenous concentrations and subcellular distribution of androgens in normal and malignant human breast tissue. Cancer Res 45: 2907–2912, 1985

    Google Scholar 

  23. Vermeulen A, Deslypere JP, Paridaens R, Leclercq G, Roy F, Heuson C: Aromatase, 17b-hydroxysteroid dehydrogenase and intratissular sex hormone concentrations in cancerous and normal glandular breast tissue in postmenopausal women. Eur J Cancer Clin Oncol 22: 515–525, 1986

    Google Scholar 

  24. Miettinen MM, Poutanen MH, Vihko RK: Characterization of estrogen-dependent growth of cultured MCF-7 human breastcancer cells expressing 17b-hydroxysteroid dehydrogenase type 1. Int J Cancer 68: 600–604, 1996

    Google Scholar 

  25. Mäentausta O, Sormunen R, Isomaa V, Lehto VP, Jouppila P, Vihko R: Immunohistochemical localization of 17b-hydroxysteroid dehydrogenase in the human endometrium during the menstrual cycle. Lab Invest 65: 582–587, 1991

    Google Scholar 

  26. Mustonen MVJ, Isomaa VV, Vaskivuo T, Tapanainen J, Poutanen MH, Stenbäck F, Vihko RK, Vihko PT: Human 17b-hydroxysteroid dehydrogenase type 2 messenger ribonucleic acid expression and localization in term placenta and in endometrium during the menstrual cycle. J Clin Endocrinol Metab 83: 1319–1324, 1998

    Google Scholar 

  27. Kaufmann M, Carstensen J, Husen B, Adamski J: The tissue distribution of porcine 17b-estradiol dehydrogenase and its induction by progesterone. J Steroid Biochem Molec Biol 55: 535–539, 1995

    Google Scholar 

  28. Markus M, Husen B, Leenders F, Jungblut PW, Hall PF, Adamski J: The organelles containing porcine 17b-estradiol dehydrogenase are peroxisomes. Eur J Cell Biol 68: 263–267, 1995

    Google Scholar 

  29. Leenders F, Tesdorpf JG, Markus M, Engel T, Seedorf U, Adamski J: Porcine 80-kDa protein reveals intrinsic 17b-hydroxysteroid dehydrogenase, fatty acyl-CoAhydratase/ dehydrogenase, and sterol transferase activities. J Biol Chem 271: 5438–5442, 1996

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miettinen, M., Mustonen, M., Poutanen, M. et al. 17β‐hydroxysteroid dehydrogenases in normal human mammary epithelial cells and breast tissue. Breast Cancer Res Treat 57, 175–182 (1999). https://doi.org/10.1023/A:1006217400137

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1006217400137

Navigation