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5α-Réductases: Physiologie et pathologie

5α-reductases=physiology and pathology

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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.

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Correspondence to Irène Mowszowicz.

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Mowszowicz, I., Berthaut, I., Mestayer, C. et al. 5α-Réductases: Physiologie et pathologie. Androl. 4, 71 (1994) doi:10.1007/BF03034623

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Mots clés

  • 5α-réductase
  • mécanisme d’action des androgènes
  • différenciation sexuelle
  • prostate
  • hirsutisme

Key words

  • 5α-reductase
  • androgen action
  • sexual différenciation
  • pseudohermaphroditism
  • idiopathic hirsutism
  • prostate