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[5-alpha-reductases: physiology and pathology]

I Mowszowicz1, I Berthauit, C Mestayer

  • 1Laboratoire de Biochimie, Hôpital Necker, Paris.

Annales D'Endocrinologie
|January 1, 1995
PubMed
Summary

5 alpha-reductase (5 alpha-R) enzymes are crucial for converting testosterone to DHT, a more potent androgen. Mutations in 5 alpha-R 2 cause male pseudohermaphroditism, while increased 5 alpha-R 1 activity may lead to androgen hypersensitivity.

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Area of Science:

  • Biochemistry
  • Genetics
  • Endocrinology

Context:

  • Androgen action in target tissues relies on 5 alpha-reduction of testosterone to dihydrotestosterone (DHT).
  • Two distinct 5 alpha-reductase (5 alpha-R) isozymes, 5 alpha-R1 and 5 alpha-R2, encoded by separate genes, have been identified.
  • These isoforms exhibit unique characteristics in terms of optimal pH, substrate/inhibitor affinities, and tissue distribution.

Purpose:

  • To elucidate the roles of 5 alpha-reductase isozymes in androgen action and related disorders.
  • To investigate the genetic basis of 5 alpha-reductase deficiency and its clinical manifestations.
  • To explore the potential involvement of 5 alpha-R1 in conditions of androgen hypersensitivity.

Summary:

  • 5 alpha-R2 is essential for sexual differentiation and prostate development; its deficiency leads to male pseudohermaphroditism in XY individuals.

Related Experiment Videos

  • Mutations in the 5 alpha-R2 gene affect enzyme activity, with specific regions implicated in substrate and cofactor binding.
  • Conversely, elevated 5 alpha-R1 activity is associated with androgen hypersensitivity, as seen in idiopathic hirsutism and benign prostatic hyperplasia.

    • Impact:

    • Understanding 5 alpha-reductase isozymes is critical for diagnosing and potentially treating disorders of sexual development and androgen-related conditions.
    • Genetic analysis of 5 alpha-R mutations provides insights into enzyme structure-function relationships.
    • This research highlights the differential roles of 5 alpha-R1 and 5 alpha-R2 in human physiology and pathology.