The DOI matches its Crossref record; 78 of the 82 references it cites were found in a registry or an index.
The Syndrome of 17,20 Lyase Deficiency
Open accessAbstract
CONTEXT: Disorders of steroidogenesis have been instrumental in delineating human steroidogenic pathways. Each genetic disorder seemed to correspond to a different steroidogenic activity, helping to identify several enzymes. Beginning in 1972, several patients have been reported as having "17,20 lyase deficiency," but there have been inconsistent genetic findings. OBJECTIVE: This manuscript reviews the biochemistry, genetics, and clinical disorders of 17,20 lyase activity, which converts 21-carbon precursors of glucocorticoids to 19-carbon precursors of sex steroids. FINDINGS: A single enzyme, cytochrome P450c17, catalyzes both 17α-hydroxylase activity and 17,20 lyase activity. The 17,20 lyase activity is especially sensitive to the activities of the accessory proteins P450 oxidoreductase and cytochrome b(5). The first cases of genetically and biochemically proven 17,20 lyase deficiency were reported in 1997, in which specific P450c17 mutations were identified that lost 17,20 lyase activity but not 17α-hydroxylase activity when assayed in vitro. Subsequent work identified other P450c17 mutations and mutations in the genes encoding P450 oxidoreductase and cytochrome b(5). Recently, the initially reported cases from 1972 were found to carry mutations in two aldo-keto reductases, AKR1C2 and AKR1C4. These AKR1C isozymes catalyze 3α-hydroxysteroid dehydrogenase activity in the so-called "backdoor pathway" by which the fetal testis produces dihydrotestosterone without the intermediacy of testosterone. CONCLUSIONS: 17,20 Lyase deficiency should be considered a syndrome with multiple causes, and not a single disease. Study of this very rare disorder has substantially advanced our understanding of the pathways, mechanisms, and control of androgen synthesis. Mutations in other, as-yet unidentified genes may also cause this phenotype.
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“Thus, the regulation of 17,20-lyase activity, and consequently of androgen production, depends on factors that facilitate the flow of electrons to P450c17: high concentrations of POR, the presence of b5, and serine phosphorylation of P450c17”
From Steroidogenic electron-transfer factors and their diseases (2021) · cites this paper as [105]
In the citing paper
“Thus, b5 deficiency is an important cause of 17,20-lyase deficiency that does not appear to affect cortisol synthesis, whereas specific P450c17 mutations and the one reported POR mutation that presented as 17,20-lyase deficiency [ 64 ] may have residual cortisol synthesis”
From Steroidogenic electron-transfer factors and their diseases (2021) · cites this paper as [105]
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Citations
Cites
The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders
Miller, W. L., & Auchus, R. J. (2011) · Endocrine Reviews · doi:10.1210/er.2010-0013 · Cited by 2,458
Genetic Control of Biochemical Reactions in Neurospora
Beadle, G. W., & Tatum, E. L. (1941) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.27.11.499 · Cited by 1,062
Role of steroidogenic acute regulatory protein in adrenal and gonadal steroidogenesis
Lin, D., Sugawara, T., Strauss, J. F., Clark, B. J., Stocco, D. M., Saenger, P., Rogol, A., & Miller, W. L. (1995) · Science · doi:10.1126/science.7892608 · Cited by 1,030
Self-citationWang, M., Roberts, D. L., Paschke, R., Shea, T. M., Masters, B. S. S., & Kim, J.-J. P. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.16.8411 · Cited by 744
The pathophysiology and genetics of congenital lipoid adrenal hyperplasia
Bose, H. S., Sugawara, T., Strauss, J. F., & Miller, W. L. (1996) · New England Journal of Medicine · doi:10.1056/nejm199612193352503 · Cited by 676
Self-citation17-Hydroxylation deficiency in man
Biglieri, E. G., Herron, M. A., & Brust, N. (1966) · Journal of Clinical Investigation · doi:10.1172/jci105499 · Cited by 561
Cytochrome b 5 Augments the 17,20-Lyase Activity of Human P450c17 without Direct Electron Transfer
Auchus, R. J., Lee, T. C., & Miller, W. L. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.6.3158 · Cited by 541
Photochemical Action Spectrum of the Terminal Oxidase of Mixed Function Oxidase Systems
Cooper, D. Y., Levin, S. S., Narasimhulu, S., Rosenthal, O., & Estabrook, R. W. (1965) · Science · doi:10.1126/science.147.3656.400 · Cited by 501
Zhang, L. H., Rodriguez, H., Ohno, S., & Miller, W. L. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.23.10619 · Cited by 455
The hormonal-control of sexual development
Wilson, J. D., George, F. W., & Griffin, J. E. (1981) · Science · doi:10.1126/science.7010602 · Cited by 451
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BindingDB Entry 50044386: Highly-selective 4-(1,2,3-triazole)-based P450c17a 17,20-lyase inhibitors.
BindingDB (2015) · UC San Diego · doi:10.7270/q2kk9dc2
Metadata
- Authors
- Miller, W. L.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Miller, Walter L.
- ORCID
- Miller, Walter L.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2012-01
- Volume
- 97
- Issue
- 1
- Pages
- 59-67
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC3251937
- OpenAlex
- W2001518235
- Cited by
- 143
- References
- 82
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 24 · 2023: 5 · 2022: 5 · 2021: 10 · 2020: 10 · 2019: 13 · 2018: 5 · 2017: 9 · 2016: 6 · 2015: 13 · 2014: 15 · 2013: 10 · 2012: 3
- FWCI
- 0.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- University of California, San Francisco
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-37922, R01DK037922)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- 17,20-lyase deficiency, steroidogenesis disorders, P450c17, cytochrome P450 oxidoreductase, cytochrome b5, AKR1C2, AKR1C4, 3α-hydroxysteroid dehydrogenase, androgen production, dihydrotestosterone
- MeSH terms
- Adrenal Hyperplasia, Congenital, Humans, Hydroxysteroid Dehydrogenases, Models, Biological, Mutation, Oxidoreductases, Steroid 17-alpha-Hydroxylase, Syndrome, Cytochromes b5, 3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)
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