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Unexpected virilization in male mice lacking steroid 5 alpha-reductase enzymes.

Mice lacking steroid 5 alpha-reductase 1 and 2 were produced by gene targeting and breeding. Male mice without 5 alpha-reductase 2 or without both enzymes had fully formed internal and external genitalia and were fertile, but had smaller prostates and seminal vesicles than controls. T accumulated to high levels in the reproductive tissues of the mutant mice. DHT administration increased seminal vesicle and coagulating gland weights in mice deficient in 5 alpha-reductase 2 and increased the weights of the prostate, seminal vesicle, and coagulating gland in animals deficient in both enzymes. An inhibitor of both 5 alpha-reductases (GI 208335X) decreased prostate and coagulating gland weights of control mice, but had no effect in those lacking 5 alpha-reductase 1 and 2. Castration reduced the sizes of these tissues in animals of all genotypes. Androgen-dependent gene expression was decreased in the seminal vesicles of mice lacking one or more 5 alpha-reductases and was restored by administration of T or DHT. Female mice missing both enzymes exhibited parturition and fecundity defects similar to those of animals without 5 alpha-reductase 1. We conclude that T is the only androgen required for differentiation of the male urogenital tract in mice and that the synthesis of DHT serves largely as a signal amplification mechanism.

Pubmed ID: 11606430


  • Mahendroo MS
  • Cala KM
  • Hess DL
  • Russell DW



Publication Data

November 18, 2001

Associated Grants

  • Agency: NICHD NIH HHS, Id: HD-38127
  • Agency: NIAMS NIH HHS, Id: R01 AR051943
  • Agency: NCRR NIH HHS, Id: RR-00163

Mesh Terms

  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase
  • 5-alpha Reductase Inhibitors
  • Androgens
  • Androstenes
  • Animals
  • Dihydrotestosterone
  • Enzyme Inhibitors
  • Female
  • Fertility
  • Genitalia, Male
  • Isoenzymes
  • Male
  • Mice
  • Mice, Knockout
  • Mutation
  • Phenotype
  • RNA, Messenger
  • Reference Values
  • Testosterone
  • Virilism