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5α-Réductases: Physiologie et pathologie

5α-reductases=physiology and pathology

Andrologie volume 4, pages 71–77 (1994)Cite this article

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Les tissus humains contiennent au moins deux isozymes de la 5α-réductase (5α-R), types 1 et 2 qui diffèrent par: leur localisation chromosomique, leur sensibilité aux inhibiteurs, leur expression tissulaire. La 5α-R2 est l’isozyme impliqué dans la différenciation sexuelle et dans le contrôle de la croissance prostatique. Elle est, dans les tissus où elle est androgéno-dépendante (prostate, peau), un amplificateur de l’action des androgènes Les anomalies de la 5α-R2 sont responsables d’insensibilités (pseudohermaphrodisme) ou d’hypersensibilités aux androgènes: hirsutisme idiopathique hyperplasie bénigne de la prostate.

Abstract

In most androgen target tissues, the first step of androgen action is the 5α-reduction of testostérone to DHT which binds to the androgen receptor wih an affinity 3 to 4 fold higher than testostérone. Two genes, encoding two isozymes of 5α-reductase (5α-R) have been cloned. The two isoforms, 5α-R1 and 5α-R2 are located on chromosome 5 and 2 respectively and differ in optimal pH, substrate and inhibitor affinities and tissue expression. 5α-R2 is responsible for sexual différenciation. It is the major form expressed in the prostate where it seems necessary for embryonic growth and development. In this tissue, as in human skin, 5α-R2 is stimulated by androgens thus amplifying androgen action. 5α-reductase deficiency results in androgen insensitivity due to abnormal 5α-R2. Affected patients are XY individuals with a very peculiar form of male pseudohermaphroditism: they have feminine genitalia at birth and masculinize at puberty. Different mutations, spannning the whole coding portion of the gene, have been described; correlation between mutations and enzyme activity have led to the tentative localization of the substrate binding site in exon 1 and the cofactor binding site in exon 4. In contrast to androgen insensitivity due to 5α-reductase deficiency, increased 5α-reductase activity can result in androgen hypersensitivity as described in idiopathic hirsutism or benign prostatic hyperplasia. In these case antiandrogen therapy, using 5α-reductase inhibitors, can be considered.

References

  1. ANDERSSON S., RUSSEL D.W.: Structural and biochemical properties of cloned and expressed human and rat steroid 5a-reductases. Proc. Natl. Acad. Sci. USA, 1990, 87: 3640–3644.

    Article  PubMed  CAS  Google Scholar 

  2. ANDERSSON S., BISCHOP R.W., RUSSELL D.W.: Expression, cloning and regulation of Steroid 5α-reductase, an enzyme essential for Male Sexual différenciation. J. Biol. Chem. 1989, 264: 16249–16255.

    PubMed  CAS  Google Scholar 

  3. ANDERSSON, S., BERMAN, D.M., JENKINS, E.P., RUSSELL, D.W.: Deletion of steroid 5α-reductase 2 gene in male pseudohermaphroditism. Nature, 1991, 354: 159–161.

    Article  PubMed  CAS  Google Scholar 

  4. BRUCHOVSKY N., WILSON J.D.: The conversion of testostérone to 5α-androstane-17β-ol-3-one by rat prostate in vivo and in vitro. J. Biol. Chem. 1968, 243: 2012–2021.

    PubMed  CAS  Google Scholar 

  5. CUSSENOT O., BERTHON PH., BERGER R., MOWSZOWICZ I., TEILLAC P., LE DUC A., CALVO F.: Immortalization of human adult normal prostatic epithelial cells by liposomes containing large T-SV40 gene. J. of Urology, 1991, 143, 881–886.

    Google Scholar 

  6. GEORGE F.W., RUSSELL D.W., WILSON J.D.: Feed-forward control of prostate growth: dihydrotestosterone induces expression of its own biosynthetic enzyme, steroid 5α-reductase. Proc. Natl. Acad Sci. USA. 1991, 88: 8044–8047.

    Article  PubMed  CAS  Google Scholar 

  7. GORMLEY G.J., STONER E., BRUSKEWITZ R.C. ET AL: The effect of finastéride in men with benign prostatic hyperplasia. N. Engl. J. Med. 1992, 327: 1185–1191.

    PubMed  CAS  Google Scholar 

  8. HODGINS, M.: Possible mechanisms of androgen resistance in 5α-reductase deficiency: implication for the physiological role of 5a-reductase. J. Steroid Biochem. 1982, 19: 555–559.

    Article  Google Scholar 

  9. JENKINS, E.P., ANDERSSON, S., IMPERATOMCGINLEY, J., WILSON, J.D., RUSSELL, D.W.: Genetic and pharmacological evidence for more than one human steroid 5α-reductase. J. Clin. Invest. 1992, 89: 293–300.

    Article  PubMed  CAS  Google Scholar 

  10. KUTTENN, F., MOWSZOWICZ, I., SCHAISON, G., MAUVAIS-JARVIS P.: Androgen production and skin metabolism in hirsutism. J. Endocr. 1977, 75: 1977, 83–91.

    Article  PubMed  CAS  Google Scholar 

  11. KUTTENN F., MOWSZOWICZ I., WRIGHT F. ET AL: Male pseudo-hermaphroditism: a comparative study of one patient with 5α-reductase deficiency and three patients with the complete form of testicular feminization. J. Clin. Endocrinol. Metab. 1979,: 1979, 861–865.

    Google Scholar 

  12. MAUVAIS-JARVIS P., MOWSZOWICZ I., KUTTENN F.: Significance of 5α-reductase activity in human sexual differentiation. In Sexual Differentiation: basic and clinical aspects. M. Serio et al Edts, Raven Press New-York, 1984, p.247–260.

    Google Scholar 

  13. MCCONNELL J.D., WILSON J.D., GEORGE F.W., GELLER J., PAPPAS F., STONER E.: finastéride an inhibitor of 5a-reductase, suppresses prostatic dihydrotestosterone in men with benign prostatic hyperplasia. J. Clin. Endocrinol. Metab. 1992, 74: 505–508.

    Article  PubMed  CAS  Google Scholar 

  14. MOORE, R.J., GRIFFIN, J.E., WILSON, J.D.: Diminished 5α-reductase activity in extracts of fibroblasts cultured from patients with familial incomplete male pseudohermaphroditism, type 2. J. Biol. Chem. 1975, 250: 7168–7172.

    PubMed  CAS  Google Scholar 

  15. MOWSZOWICZ I., MELANITOU E., KIRCHHOFFER M.O., MAUVAIS-JARVIS P.: Dihydrotestosterone stimulates 5a-reductase activity in pubic skin fibroblasts. J. Clin. Endocrinol. Metab. 1983, 56: 320–325.

    PubMed  CAS  Google Scholar 

  16. MOWSZOWICZ I., RIAHI M., WRIGHT F., BOUCHARD PH., KUTTENN F., MAUVAIS-JARVIS P.: Androgen receptor in human skin cytosol. J. Clin. Endocrinol. Metab. 1981, 52: 338–344.

    Article  PubMed  CAS  Google Scholar 

  17. PETERSON R.E., IMPERATO-MCGINLEY J., GAUTIER T. AND STURLA E.: Male pseudohermaphroditism due to steroid 5α-reductase deficiency. Amer. J. Med. 1977, 62: 170–191.

    Article  PubMed  CAS  Google Scholar 

  18. SIITERI P.K., WILSON J.D.: testostérone formation and metabolism during male sexual differentiation in the human embryo. J. Clin. Endocrinol. Metab. 1974, 38: 113–125.

    PubMed  CAS  Google Scholar 

  19. THIGPEN A.E., DAVIS D.L., MILATOVICH A. ET AL: Molecular genetics of steroid 5α-Reductase 2 deficiency. J. Clin. Invest. 1992, 90: 799–809.

    Article  PubMed  CAS  Google Scholar 

  20. THIGPEN A.E., RUSSEL D.W.: Four-amino acid segment in steroid 5α-reductase 1 confers sensitivity to finastéride, a competitive inhibitor. J. Biol. Chem. 1992, 267: 8577–8583.

    PubMed  CAS  Google Scholar 

  21. THIGPEN A.E., SILVER R.I., GUILEYARDO J.M., CASEY M.L., MCCONNELL J.D., RUSSEL D.W.: Tissue distribution and ontogeny of steroid 5a-reductase isozyme expression. J. Clin. Invest. 1993, 92: 903–910.

    Article  PubMed  CAS  Google Scholar 

  22. VOIGT W., HSIA S.L.: Further studies on testostérone 5α-reductase of human skin. Structural features of steroid inhibitors. J. Biol. Chem. 1973, 248: 4280–4285.

    PubMed  CAS  Google Scholar 

  23. WILSON J.D., GRIFFIN J.E., RUSSELL D.W.: Steroid 5α-reductase deficiency. Endocr. Rev. 1993, 14: 577–593.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Laboratoire de Biochimie B, HÔpital Necker, Paris

    Irène Mowszowicz & Isabelle Berthaut

  2. Service d’Endocrinologie et de Médecine de la Reproduction, Hôpital Necker, Paris

    Irène Mowszowicz, Frédérique Kuttenn & Pierre Mauvais-Jarvis

  3. Service de Biochimie Médicale, Faculté de Médecine Pitié-Salpêtrière, Paris

    Chidi Mestayer & Françoise Wright

Authors
  1. Irène Mowszowicz
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  2. Isabelle Berthaut
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  3. Chidi Mestayer
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  4. Françoise Wright
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  5. Frédérique Kuttenn
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  6. Pierre Mauvais-Jarvis
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Mowszowicz, I., Berthaut, I., Mestayer, C. et al. 5α-Réductases: Physiologie et pathologie. Androl. 4, 71–77 (1994). https://doi.org/10.1007/BF03034623

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Basic and Clinical Andrology

ISSN: 2051-4190