SRD5A1

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Protein-coding gene in the species Homo sapiens

title: "SRD5A1" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public description: "Protein-coding gene in the species Homo sapiens" topic_path: "uncategorized" source: "https://en.wikipedia.org/wiki/SRD5A1" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Protein-coding gene in the species Homo sapiens ::

3-Oxo-5α-steroid 4-dehydrogenase 1 is an enzyme that in humans is encoded by the SRD5A1 gene. It is one of three forms of steroid 5α-reductase.

Steroid 5α-reductase (EC 1.3.99.5) catalyzes, among other reactions, the conversion of testosterone into the more potent androgen, 5α-dihydrotestosterone (DHT). The SRD5A1, SRD5A2, and SRD5A3 genes in humans all encode 5α-reductase isozymes.

Function

Main article: 5α-Reductase

The 3-oxo-5α-steroid 4-dehydrogenase 1 enzyme is involved in bile acid biosynthesis, androgen and estrogen metabolism. For instance, the enzyme catalyzes the conversion of testosterone into the more potent androgen, 5α-dihydrotestosterone. It can also catalyze the conversion of progesterone, corticosterone or other steroids, to its corresponding 5α-3-oxo-steroids. This chemical reaction is called 5α-reduction, i.e. the reduction of the Δ5-4 double bond in steroids by catalyzing direct hydride transfer from NADPH to the carbon 5 position of the steroid substrate.

Regulation

The SRD5A1 gene is particularly susceptible to epigenetic regulation, and responsive to environmental stressors at key stages during postnatal development. This regulation leads to increased DNA methylation at the gene's intronic enhancer, and its reduced expression, which have lasting effects on reproductive function.

ETV4 family members bind to ETS DNA-binding sites and both regulate their own expression and the transcription of a subset of genes that are dependent upon testicular luminal fluid factors, including Ggt_pr4, SRD5A1, and Gpx5.

Six-month dietary vitamin E deficiency in rats resulted in a twofold increase in the mRNA level of SRD5A1 gene and a twofold decrease in the mRNA level of GCLM gene but is not directly mediated by changes in promoter DNA methylation.

Insulin increases the expression of 5α-reductase type 1 mRNA via Akt signalling suggest that elevated levels of 5α-reduced androgens seen in hyperinsulinemic conditions might be explained on the basis of a stimulatory effect of insulin on 5α-reductase in granulosa cells leading to impaired follicle growth and ovulation.

Clinical significance

Hyperinsulinemia acutely enhances ACTH effects on both the androgen and glucocorticoid pathways leading to changes in steroid metabolites molar ratios that suggest insulin stimulation of 5α-reductase activity.

PCOS is associated with enhanced androgen and cortisol metabolite excretion and increased 5α-reductase activity that cannot be explained by obesity alone. Increased adrenal corticosteroid production represents an important pathogenic pathway in PCOS.

Progression to castration-resistant prostate cancer (CRPC) is accompanied by increased expression of SRD5A1 over SRD5A2, which is otherwise the dominant isoenzyme expressed in the prostate. The dominant route of DHT synthesis in human CRPC bypasses testosterone, and instead requires 5α-reduction of androstenedione by SRD5A1 to 5α-androstanedione, which is then converted to DHT fuelling cancer growth.

Expression

::figure[src="https://upload.wikimedia.org/wikipedia/commons/8/80/SRD5A1-human-tissue-expression-pmid24309898.svg" caption="url-status=live}} The FPKM data is taken from a 2014 study."] ::

In humans, the protein isozyme encoded by the SRD5A1 gene is expressed in esophagus, liver, skin and 24 other tissues.

References

References

  1. (December 1991). "Characterization and chromosomal mapping of a human steroid 5 alpha-reductase gene and pseudogene and mapping of the mouse homologue". Genomics.
  2. "Entrez Gene: SRD5A1 steroid-5-alpha-reductase, alpha polypeptide 1 (3-oxo-5 alpha-steroid delta 4-dehydrogenase alpha 1)".
  3. (February 2012). "5α-Reduced glucocorticoids: a story of natural selection". The Journal of Endocrinology.
  4. (2012). "The 5 alpha-reductase isozyme family: a review of basic biology and their role in human diseases". Advances in Urology.
  5. (January 2021). "Crystal structure of steroid reductase SRD5A reveals conserved steroid reduction mechanism". Nature Communications.
  6. (January 2022). "Epigenetic regulation of 5α reductase-1 underlies adaptive plasticity of reproductive function and pubertal timing". BMC Biology.
  7. (August 2023). "Srd5a1 is Differentially Regulated and Methylated During Prepubertal Development in the Ovary and Hypothalamus". Journal of the Endocrine Society.
  8. (April 2006). "Putative regulation of expression of members of the Ets variant 4 transcription factor family and their downstream targets in the rat epididymis". Biology of Reproduction.
  9. (October 2010). "Dietary vitamin E deficiency does not affect global and specific DNA methylation patterns in rat liver". The British Journal of Nutrition.
  10. (October 2010). "Stimulatory effect of insulin on 5alpha-reductase type 1 (SRD5A1) expression through an Akt-dependent pathway in ovarian granulosa cells". Endocrinology.
  11. (February 2011). "Insulin enhances ACTH-stimulated androgen and glucocorticoid metabolism in hyperandrogenic women". European Journal of Endocrinology.
  12. (September 2009). "Increased 5 alpha-reductase activity and adrenocortical drive in women with polycystic ovary syndrome". The Journal of Clinical Endocrinology and Metabolism.
  13. (August 2011). "Dihydrotestosterone synthesis bypasses testosterone to drive castration-resistant prostate cancer". Proceedings of the National Academy of Sciences of the United States of America.
  14. (2 May 2014). "What the FPKM? A review of RNA-Seq expression units".
  15. "SRD5A1 steroid 5 alpha-reductase 1 - Homo sapiens (human) - expression".
  16. (February 2014). "Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics". Molecular & Cellular Proteomics.

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