5α-reduced androgens play a key role in murine parturition

Research output: Contribution to journalArticle

167 Citations (Scopus)

Abstract

Two steroid 5α-reductase isozymes designated type 1 and 2 synthesize 5α- reduced androgens and other 5α-reduced steroid hormones. Naturally occurring mutations in the gene encoding 5α-reductase type 2 cause male pseudohermaphroditism, indicating that this isozyme is responsible for the synthesis of dihydrotestosterone required for virilization of the embryonic male urogenital tract. To determine the physiological role of 5α-reductase type 1, homologous recombination in mouse embryonic stem cells was used to produce male and female mice with a disruption (null allele) in the type 1 gene (Srd5a1). Male mice lacking 5α-reductase type 1 appear normal. Females exhibit a parturition defect that is maternal in origin. The parturition defect is reversed by administration of 5α-androstan-3α,17β-diol (3α- Adiol), a 5α-reduced androgen previously thought to be a breakdown product. Enzymes that synthesize 3α-Adiol, including 5α-reductase type 1 and 3α- hydroxysteroid dehydrogenase, are induced in wild type uterus during late gestation. Induction leads to peak circulating levels of 3α-Adiol on days 17/18 of gestation in wild type but not mutant mice. The results document a role for 5α-reduced androgens synthesized by the type 1 isozyme in normal female physiology, and they suggest that 3α-Adiol is a new hormone required for parturition in mice.

Original languageEnglish (US)
Pages (from-to)380-392
Number of pages13
JournalMolecular Endocrinology
Volume10
Issue number4
DOIs
StatePublished - 1996

Fingerprint

Androgens
Oxidoreductases
Parturition
Isoenzymes
3-Hydroxysteroid Dehydrogenases
Steroids
XY Disorders of Sex Development 46
Hormones
Virilism
Pregnancy
Dihydrotestosterone
Homologous Recombination
Genes
Uterus
Alleles
Mothers
Mutation
Enzymes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

5α-reduced androgens play a key role in murine parturition. / Mahendroo, Mala S.; Cala, Kristine M.; Russell, David W.

In: Molecular Endocrinology, Vol. 10, No. 4, 1996, p. 380-392.

Research output: Contribution to journalArticle

@article{099a40a62d224332b0ea880b21c67fa2,
title = "5α-reduced androgens play a key role in murine parturition",
abstract = "Two steroid 5α-reductase isozymes designated type 1 and 2 synthesize 5α- reduced androgens and other 5α-reduced steroid hormones. Naturally occurring mutations in the gene encoding 5α-reductase type 2 cause male pseudohermaphroditism, indicating that this isozyme is responsible for the synthesis of dihydrotestosterone required for virilization of the embryonic male urogenital tract. To determine the physiological role of 5α-reductase type 1, homologous recombination in mouse embryonic stem cells was used to produce male and female mice with a disruption (null allele) in the type 1 gene (Srd5a1). Male mice lacking 5α-reductase type 1 appear normal. Females exhibit a parturition defect that is maternal in origin. The parturition defect is reversed by administration of 5α-androstan-3α,17β-diol (3α- Adiol), a 5α-reduced androgen previously thought to be a breakdown product. Enzymes that synthesize 3α-Adiol, including 5α-reductase type 1 and 3α- hydroxysteroid dehydrogenase, are induced in wild type uterus during late gestation. Induction leads to peak circulating levels of 3α-Adiol on days 17/18 of gestation in wild type but not mutant mice. The results document a role for 5α-reduced androgens synthesized by the type 1 isozyme in normal female physiology, and they suggest that 3α-Adiol is a new hormone required for parturition in mice.",
author = "Mahendroo, {Mala S.} and Cala, {Kristine M.} and Russell, {David W.}",
year = "1996",
doi = "10.1210/me.10.4.380",
language = "English (US)",
volume = "10",
pages = "380--392",
journal = "Molecular Endocrinology",
issn = "0888-8809",
publisher = "The Endocrine Society",
number = "4",

}

TY - JOUR

T1 - 5α-reduced androgens play a key role in murine parturition

AU - Mahendroo, Mala S.

AU - Cala, Kristine M.

AU - Russell, David W.

PY - 1996

Y1 - 1996

N2 - Two steroid 5α-reductase isozymes designated type 1 and 2 synthesize 5α- reduced androgens and other 5α-reduced steroid hormones. Naturally occurring mutations in the gene encoding 5α-reductase type 2 cause male pseudohermaphroditism, indicating that this isozyme is responsible for the synthesis of dihydrotestosterone required for virilization of the embryonic male urogenital tract. To determine the physiological role of 5α-reductase type 1, homologous recombination in mouse embryonic stem cells was used to produce male and female mice with a disruption (null allele) in the type 1 gene (Srd5a1). Male mice lacking 5α-reductase type 1 appear normal. Females exhibit a parturition defect that is maternal in origin. The parturition defect is reversed by administration of 5α-androstan-3α,17β-diol (3α- Adiol), a 5α-reduced androgen previously thought to be a breakdown product. Enzymes that synthesize 3α-Adiol, including 5α-reductase type 1 and 3α- hydroxysteroid dehydrogenase, are induced in wild type uterus during late gestation. Induction leads to peak circulating levels of 3α-Adiol on days 17/18 of gestation in wild type but not mutant mice. The results document a role for 5α-reduced androgens synthesized by the type 1 isozyme in normal female physiology, and they suggest that 3α-Adiol is a new hormone required for parturition in mice.

AB - Two steroid 5α-reductase isozymes designated type 1 and 2 synthesize 5α- reduced androgens and other 5α-reduced steroid hormones. Naturally occurring mutations in the gene encoding 5α-reductase type 2 cause male pseudohermaphroditism, indicating that this isozyme is responsible for the synthesis of dihydrotestosterone required for virilization of the embryonic male urogenital tract. To determine the physiological role of 5α-reductase type 1, homologous recombination in mouse embryonic stem cells was used to produce male and female mice with a disruption (null allele) in the type 1 gene (Srd5a1). Male mice lacking 5α-reductase type 1 appear normal. Females exhibit a parturition defect that is maternal in origin. The parturition defect is reversed by administration of 5α-androstan-3α,17β-diol (3α- Adiol), a 5α-reduced androgen previously thought to be a breakdown product. Enzymes that synthesize 3α-Adiol, including 5α-reductase type 1 and 3α- hydroxysteroid dehydrogenase, are induced in wild type uterus during late gestation. Induction leads to peak circulating levels of 3α-Adiol on days 17/18 of gestation in wild type but not mutant mice. The results document a role for 5α-reduced androgens synthesized by the type 1 isozyme in normal female physiology, and they suggest that 3α-Adiol is a new hormone required for parturition in mice.

UR - http://www.scopus.com/inward/record.url?scp=0029990372&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029990372&partnerID=8YFLogxK

U2 - 10.1210/me.10.4.380

DO - 10.1210/me.10.4.380

M3 - Article

C2 - 8721983

AN - SCOPUS:0029990372

VL - 10

SP - 380

EP - 392

JO - Molecular Endocrinology

JF - Molecular Endocrinology

SN - 0888-8809

IS - 4

ER -