5 alpha-reduced androgens play a key role in murine parturition.
Abstract
Two steroid 5 alpha-reductase isozymes designated type 1 and 2 synthesize 5 alpha-reduced androgens and other 5 alpha-reduced steroid hormones. Naturally occurring mutations in the gene encoding 5 alpha-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 5 alpha-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 5 alpha-reductase type 1 appear normal. Females exhibit a parturition defect that is maternal in origin. The parturition defect is reversed by administration of 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha-Adiol), a 5 alpha-reduced androgen previously thought to be a breakdown product. Enzymes that synthesize 3 alpha-Adiol, including 5 alpha-reductase type 1 and 3 alpha-hydroxysteroid dehydrogenase, are induced in wild type uterus during late gestation. Induction leads to peak circulating levels of 3 alpha-Adiol on days 17/18 of gestation in wild type but not mutant mice. The results document a role for 5 alpha-reduced androgens synthesized by the type 1 isozyme in normal female physiology, and they suggest that 3 alpha-Adiol is a new hormone required for parturition in mice.
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Disruption of the mouse srd5a1 gene results in delayed parturition, which can be rescued with 5α-androstane-3α,17β-diol.
“However, disruption of the corresponding mouse srd5a1 gene results in delayed parturition, which can be rescued with 5␣-androstane-3␣,17-diol (555).”
From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [555]
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- Authors
- Mahendroo, M. S., Cala, K. M., & Russell, D. W.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1996-04
- Volume
- 10
- Issue
- 4
- Pages
- 380-392
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- OpenAlex
- W1972414087
- Cited by
- 204
- References
- 1
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 7 · 2021: 5 · 2020: 3 · 2019: 5 · 2018: 1 · 2017: 3 · 2016: 6 · 2015: 2 · 2014: 15 · 2013: 5 · 2012: 11
- FWCI
- 6.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01gm043753-07, 1f32gm016292-01)
- National Institute of General Medical Sciences (GM-16292, GM-43753)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- childbirth, SRD5A1, uterus, 3α-hydroxysteroid dehydrogenase, gestation, female reproductive physiology, dihydrotestosterone
- MeSH terms
- Androgens, Animals, Blastocyst, Crosses, Genetic, Exons, Female, Genotype, Labor, Obstetric, Male, Mice, Inbred C57BL, Mice, Inbred Strains, Mutation, Oxidation-Reduction, Oxidoreductases, Pregnancy, Sex Differentiation, Disorders of Sex Development, Stem Cells, Gene Expression, Cholestenone 5 alpha-Reductase, Mice
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