Unexpected virilization in male mice lacking steroid 5α-reductase enzymes

Mala S. Mahendroo, Kristi M. Cala, David Hess, David W. Russell

    Research output: Contribution to journalArticle

    95 Citations (Scopus)

    Abstract

    Mice lacking steroid 5α-reductase 1 and 2 were produced by gene targeting and breeding. Male mice without 5α-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 5α-reductase 2 and increased the weights of the prostate, seminal vesicle, and coagulating gland in animals deficient in both enzymes. An inhibitor of both 5α-reductases (GI208335X) decreased prostate and coagulating gland weights of control mice, but had no effect in those lacking 5α-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 5α-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 5α-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.

    Original languageEnglish (US)
    Pages (from-to)4652-4662
    Number of pages11
    JournalEndocrinology
    Volume142
    Issue number11
    DOIs
    StatePublished - 2001

    Fingerprint

    Virilism
    Oxidoreductases
    Steroids
    Seminal Vesicles
    Enzymes
    Prostate
    Weights and Measures
    Androgens
    Genitalia
    Gene Targeting
    Castration
    Breeding
    Fertility
    Genotype
    Parturition
    Gene Expression

    ASJC Scopus subject areas

    • Endocrinology
    • Endocrinology, Diabetes and Metabolism

    Cite this

    Mahendroo, M. S., Cala, K. M., Hess, D., & Russell, D. W. (2001). Unexpected virilization in male mice lacking steroid 5α-reductase enzymes. Endocrinology, 142(11), 4652-4662. https://doi.org/10.1210/en.142.11.4652

    Unexpected virilization in male mice lacking steroid 5α-reductase enzymes. / Mahendroo, Mala S.; Cala, Kristi M.; Hess, David; Russell, David W.

    In: Endocrinology, Vol. 142, No. 11, 2001, p. 4652-4662.

    Research output: Contribution to journalArticle

    Mahendroo, MS, Cala, KM, Hess, D & Russell, DW 2001, 'Unexpected virilization in male mice lacking steroid 5α-reductase enzymes', Endocrinology, vol. 142, no. 11, pp. 4652-4662. https://doi.org/10.1210/en.142.11.4652
    Mahendroo, Mala S. ; Cala, Kristi M. ; Hess, David ; Russell, David W. / Unexpected virilization in male mice lacking steroid 5α-reductase enzymes. In: Endocrinology. 2001 ; Vol. 142, No. 11. pp. 4652-4662.
    @article{28c78afff00b4479b51e0eb14368932e,
    title = "Unexpected virilization in male mice lacking steroid 5α-reductase enzymes",
    abstract = "Mice lacking steroid 5α-reductase 1 and 2 were produced by gene targeting and breeding. Male mice without 5α-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 5α-reductase 2 and increased the weights of the prostate, seminal vesicle, and coagulating gland in animals deficient in both enzymes. An inhibitor of both 5α-reductases (GI208335X) decreased prostate and coagulating gland weights of control mice, but had no effect in those lacking 5α-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 5α-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 5α-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.",
    author = "Mahendroo, {Mala S.} and Cala, {Kristi M.} and David Hess and Russell, {David W.}",
    year = "2001",
    doi = "10.1210/en.142.11.4652",
    language = "English (US)",
    volume = "142",
    pages = "4652--4662",
    journal = "Endocrinology",
    issn = "0013-7227",
    publisher = "The Endocrine Society",
    number = "11",

    }

    TY - JOUR

    T1 - Unexpected virilization in male mice lacking steroid 5α-reductase enzymes

    AU - Mahendroo, Mala S.

    AU - Cala, Kristi M.

    AU - Hess, David

    AU - Russell, David W.

    PY - 2001

    Y1 - 2001

    N2 - Mice lacking steroid 5α-reductase 1 and 2 were produced by gene targeting and breeding. Male mice without 5α-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 5α-reductase 2 and increased the weights of the prostate, seminal vesicle, and coagulating gland in animals deficient in both enzymes. An inhibitor of both 5α-reductases (GI208335X) decreased prostate and coagulating gland weights of control mice, but had no effect in those lacking 5α-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 5α-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 5α-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.

    AB - Mice lacking steroid 5α-reductase 1 and 2 were produced by gene targeting and breeding. Male mice without 5α-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 5α-reductase 2 and increased the weights of the prostate, seminal vesicle, and coagulating gland in animals deficient in both enzymes. An inhibitor of both 5α-reductases (GI208335X) decreased prostate and coagulating gland weights of control mice, but had no effect in those lacking 5α-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 5α-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 5α-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.

    UR - http://www.scopus.com/inward/record.url?scp=0034750057&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=0034750057&partnerID=8YFLogxK

    U2 - 10.1210/en.142.11.4652

    DO - 10.1210/en.142.11.4652

    M3 - Article

    C2 - 11606430

    AN - SCOPUS:0034750057

    VL - 142

    SP - 4652

    EP - 4662

    JO - Endocrinology

    JF - Endocrinology

    SN - 0013-7227

    IS - 11

    ER -