Structural and biochemical properties of cloned and expressed human and rat steroid 5 alpha-reductases
Open accessAbstract
The microsomal enzyme steroid 5 alpha-reductase is responsible for the conversion of testosterone into the more potent androgen dihydrotestosterone. In man, this steroid acts on a variety of androgen-responsive target tissues to mediate such diverse endocrine processes as male sexual differentiation in the fetus and prostatic growth in men. Here we describe the isolation, structure, and expression of a cDNA encoding the human steroid 5 alpha-reductase. A rat cDNA was used as a hybridization probe to screen a human prostate cDNA library. A 2.1-kilobase cDNA was identified and DNA sequence analysis indicated that the human steroid 5 alpha-reductase was a hydrophobic protein of 259 amino acids with a predicted molecular weight of 29,462. A comparison of the human and rat protein sequences revealed a 60% identity. Transfection of expression vectors containing the human and rat cDNAs into simian COS cells resulted in the synthesis of high levels of steroid 5 alpha-reductase enzyme activity. Both enzymes expressed in COS cells showed similar substrate specificities for naturally occurring steroid hormones. However, synthetic 4-azasteroids demonstrated marked differences in their abilities to inhibit the human and rat steroid 5 alpha-reductases.
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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 [14]
SRD5A1 catalyzes 5α-reduction of A4 more efficiently than that of testosterone.
“Indeed, the enzyme steroid 5α-reductase 1 (SRD5A1) catalyzes the 5α-reduction of A4 more efficiently than that of testosterone [56,57].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [57]
SRD5As and AKR1D1 exhibit different catalytic efficiencies towards structurally different steroids.
“SRD5As and AKR1D1 exhibit different catalytic efficiencies towards structurally different steroids [57,100]”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [57]
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- Authors
- Andersson, S., & Russell, D. W.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- ORCID
- Russell, D W
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1990-05
- Volume
- 87
- Issue
- 10
- Pages
- 3640-3644
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC53958
- OpenAlex
- W2022065845
- Cited by
- 501
- References
- 21
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 6 · 2023: 6 · 2022: 6 · 2021: 5 · 2020: 7 · 2019: 6 · 2018: 9 · 2017: 6 · 2016: 11 · 2015: 13 · 2014: 10 · 2013: 14 · 2012: 10
- FWCI
- 16.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01gm043753-07)
- National Institute of General Medical Sciences (GM-43753)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Health Sciences › Medicine › Urology › Urinary Bladder and Prostate Research
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- 5α-reductase, cDNA cloning, testosterone, microsomal enzymes, prostate, enzyme inhibition, substrate specificity, protein structure, male sexual differentiation, prostate enlargement
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Cell Line, Cloning, Molecular, DNA, Genetic Vectors, Humans, Kinetics, Molecular Sequence Data, Sequence Homology, Nucleic Acid, Substrate Specificity, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase, Transfection, Oligonucleotide Probes, Gene Expression, Polymerase Chain Reaction, Rats
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