Tissue distribution and ontogeny of steroid 5 alpha-reductase isozyme expression.
Open accessAbstract
The synthesis of dihydrotestosterone is catalyzed by steroid 5 alpha-reductase isozymes, designated types 1 and 2. Mutation of type 2 results in male pseudohermaphroditism, in which the external genitalia are phenotypically female at birth. Two striking and unexplained features of this disorder are that external genitalia of affected males undergo virilization during puberty and that these individuals have less temporal hair regression. The tissue-specific and developmental expression patterns of the 5 alpha-reductase isozymes were investigated by immunoblotting. The type 1 isozyme is not detectable in the fetus, is transiently expressed in newborn skin and scalp, and permanently expressed in skin from the time of puberty. There was no qualitative difference in 5 alpha-reductase type 1 expression between adult balding vs. nonbalding scalp. The type 2 isozyme is transiently expressed in skin and scalp of newborns. Type 2 is the predominant isozyme detectable in fetal genital skin, male accessory sex glands, and in the prostate, including benign prostatic hyperplasia and prostate adenocarcinoma tissues. Both isozymes are expressed in the liver, but only after birth. These results are consistent with 5 alpha-reductase type 1 being responsible for virilization in type 2-deficient subjects during puberty, and suggest that the type 2 isozyme may be an initiating factor in development of male pattern baldness.
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SRD5A1 is not expressed in the fetus, which explains why fetal deficiency of the type 2 enzyme is not compensated for by the type 1 enzyme.
“SRD5A1 is not expressed in the fetus, which explains why fetal deficiency of the type 2 enzyme is not compensated for by the type 1 enzyme (550).”
From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [550]
The type 1 enzyme may be responsible for the pubertal virilization seen in patients with classic 5α-reductase deficiency, and the type 2 enzyme may be involved in male pattern baldness.
“Thus, the type 1 enzyme may be responsible for the pubertal virilization seen in patients with classic 5␣-reductase deficiency, and the type 2 enzyme may be involved in male pattern baldness (550).”
From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [550]
Estradiol, dihydrotestosterone, and 3-alpha androstanediol have established roles in reproductive, bone, hepatic, renal, cardiovascular, dermatologic, prostatic, penile, and central nervous system functions.
“Estradiol, DHT, and the DHT product, 3-alpha androstanediol have established roles in reproductive, bone, hepatic, renal, cardiovascular, dermatologic, prostatic, penile, and central nervous system functions, among others.”
From Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials (2016) · cites this paper as [16]
SRD5A1 is mainly expressed in the liver and peripheral tissues.
“SRD5A1 is mainly expressed in the liver and peripheral tissues [94]”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [94]
Androgens and precursors that escape tissue-specific activation via 5α-reduction are metabolized within the liver, which expresses both 5α- and 5β-reductases.
“Those androgens and precursors that escape the tissue specific activation via 5α-reduction are metabolized within the liver, which expresses both 5α- and 5β-reductases [54,94,100].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [94]
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- Authors
- Thigpen, A. E., Silver, R. I., Guileyardo, J. M., Casey, M. L., McConnell, J. D., & Russell, D. W.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- ORCID
- Russell, D W
- Venue
- Journal of Clinical Investigation
- Published
- 1993-08-01
- Volume
- 92
- Issue
- 2
- Pages
- 903-910
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC294929
- OpenAlex
- W2081251422
- Semantic Scholar
- 0c528f6c738bfa41ffc5d11368359cdfb4fa4bd3
- Cited by
- 727
- References
- 40
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 15 · 2023: 14 · 2022: 14 · 2021: 13 · 2020: 18 · 2019: 24 · 2018: 14 · 2017: 16 · 2016: 12 · 2015: 27 · 2014: 26 · 2013: 23 · 2012: 25
- FWCI
- 8.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Welch Foundation
- University of Texas Southwestern Medical Center
- National Institutes of Health (5r01gm043753-07)
- National Institute of General Medical Sciences (GM-43753)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 07504)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- 5α-reductase, 5α-reductase type 1, 5α-reductase type 2, dihydrotestosterone, androgen production, 46,XY disorders of sex development, 5-alpha-reductase deficiency, masculinization, androgenetic alopecia, scalp hair, tissue distribution, ontogeny, prostate, benign prostatic hyperplasia, prostate adenocarcinoma, liver, male accessory sex glands
- MeSH terms
- Adenocarcinoma, Aging, Alopecia, Animals, Brain, Fetus, Genitalia, Male, Cricetinae, Humans, Infant, Newborn, Isoenzymes, Kinetics, Liver, Male, Organ Specificity, Prostatic Hyperplasia, Prostatic Neoplasms, Puberty, RNA, Messenger, Scalp, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase, Immunoblotting, Gene Expression Regulation, Enzymologic, CHO Cells
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