Aromatase: Wikis


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Cytochrome P450, family 19, subfamily A, polypeptide 1

Crystallographic structure of the human aromatase cytochrome P450 (rainbow colored cartoon, N-terminus = blue, C-terminus = red) in complex with the cofactor protoporphyrin IX (top) and the substrate androstenedione (bottom) depicted as stick diagrams (carbon = white, oxygen = red, nitrogen = blue, iron = orange).[1]
Available structures
Symbols CYP19A1; ARO; ARO1; CPV1; CYAR; CYP19; MGC104309; P-450AROM
External IDs OMIM107910 MGI88587 HomoloGene30955 GeneCards: CYP19A1 Gene
EC number
RNA expression pattern
PBB GE CYP19A1 203475 at tn.png
More reference expression data
Species Human Mouse
Entrez 1588 13075
Ensembl ENSG00000137869 ENSMUSG00000032274
UniProt P11511 Q3ZAT3
RefSeq (mRNA) NM_000103 NM_007810
RefSeq (protein) NP_000094 NP_031836
Location (UCSC) Chr 15:
49.29 - 49.4 Mb
Chr 9:
53.96 - 53.99 Mb
PubMed search [1] [2]

Aromatase is an enzyme that is responsible for a key step in the biosynthesis of estrogens. Because estrogens also promote certain cancers and other diseases, aromatase inhibitors are frequently used to treat those diseases.

Steroids are composed of four fused rings (labeled A, B, C, and D in the figure below). Aromatase transforms the left-hand ring (the A-ring) of steroids to an aromatic state (hence the name) through oxidation and subsequent elimination of a methyl group.

Aromatase converts testosterone to estradiol

Aromatase is a member of the cytochrome P450 superfamily (EC, whose function is to aromatize androgens, producing estrogens. As such, it is an important factor in sexual development.



Mechanism of the chemical reaction catalyzed by the aromatase enzyme.[2]
Steroidogenesis, showing both actions of aromatase at bottom center.

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and catalyzes the last steps of estrogen biosynthesis from androgens. These steps include three successive hydroxylations of the 19-methyl group of androgens followed by simultaneous elimination of the methyl group as formate and aromatization of the A-ring. Mutations in this gene can result in either increased or decreased aromatase activity; the associated phenotypes suggest that estrogen functions both as a sex steroid hormone and in growth or differentiation. The gene expresses two transcript variants.[3]


In humans, the gene CYP19, located on chromosome 15q21.1, encodes the aromatase enzyme.[4] CYP19 is present in an early-diverging chordate, the cephalochordate amphioxus (the Florida lancelet, Branchiostoma floridae), but not in the earlier diverging tunicate Ciona intestinalis. Thus the aromatase gene evolved early in chordate evolution and does not appear to be present in non-chordate invertebrates (e.g. insects, molluscs, echinoderms, sponges, corals). However, estrogens may be synthesized in some of these organisms, via other unknown pathways.

Cellular and tissue location

The enzyme is located in the endoplasmic reticulum of the cell and its activity is regulated by tissue specific promoters that are in turn controlled by hormones, cytokines, and other factors. The principal action of the enzyme transforms androstenedione to estrone and testosterone to estradiol. The aromatase enzyme can be found in many tissues including gonads, brain, adipose tissue, placenta, blood vessels, skin, bone, endometrium as well as in tissue of endometriosis, uterine fibroids, breast cancer, and endometrial cancer.


Factors known to increase aromatase activity include age, obesity, insulin, gonadotropins, and alcohol. Aromatase activity is decreased by prolactin, anti-müllerian hormone, and smoking. Aromatase activity appears to be enhanced in certain estrogen-dependent local tissue next to breast tissue, endometrial cancer, endometriosis, and uterine fibroids.



Aromatase excess syndrome

A number of investigators have reported on a rather rare syndrome of excess aromatase activity. In boys it can lead to gynecomastia and in girls to precocious puberty and gigantomastia. In both sexes, early epiphyseal closure leads to shortness.

Aromatase deficiency syndrome

This syndrome is due to a mutation of gene CYP19 and inherited in an autosomal recessive way. Accumulations of androgens during pregnancy may lead to virilization of a female at birth (males are not affected). Females will have primary amenorrhea. Individuals of both sexes will be tall as lack of estrogen does not bring the epiphyseal lines to closure.

Aromatase inhibitors

The inhibition of the enzyme leads to profound hypoestrogenism (low estrogen levels). Thus aromatase inhibitors have become useful in the management of patients with breast cancer whose lesion was found to be estrogen receptor positive. An example of an aromatase inhibitor is letrozole, marketed originally under the name 'Femara.'

Extracts of certain mushrooms can inhibit aromatase.[5]


  1. ^ PDB 3EQM; Ghosh D, Griswold J, Erman M, Pangborn W (January 2009). "Structural basis for androgen specificity and oestrogen synthesis in human aromatase". Nature 457 (7226): 219–23. doi:10.1038/nature07614. PMID 19129847.  
  2. ^ Vaz ADN (2003). "Chapter 1: Cytochrome activation by cytochromes P450: a role for multiple oxidants in the oxidation of substrates". in Fisher, Michael; Lee, Jae Kyu; Obach, Robert E.. Drug metabolizing enzymes: cytochrome P450 and other enzymes in drug discovery and development. Lausanne, Switzerland: FontisMedia SA. ISBN 0-8247-4293-1.  
  3. ^ "Entrez Gene: CYP19A1 cytochrome P450, family 19, subfamily A, polypeptide 1".  
  4. ^ Toda K, Shizuta Y (April 1993). "Molecular cloning of a cDNA showing alternative splicing of the 5'-untranslated sequence of mRNA for human aromatase P-450". Eur. J. Biochem. 213 (1): 383–9. doi:10.1111/j.1432-1033.1993.tb17772.x. PMID 8477708.  
  5. ^ Chen S, Oh SR, Phung S, Hur G, Ye JJ, Kwok SL, Shrode GE, Belury M, Adams LS, Williams D (December 2006). "Anti-aromatase activity of phytochemicals in white button mushrooms (Agaricus bisporus)". Cancer Res. 66 (24): 12026–34. doi:10.1158/0008-5472.CAN-06-2206. PMID 17178902.  

Further reading

  • Attar E, Bulun SE (May 2006). "Aromatase inhibitors: the next generation of therapeutics for endometriosis?". Fertil. Steril. 85 (5): 1307–18. doi:10.1016/j.fertnstert.2005.09.064. PMID 16647373.  
  • Chen S (2004). "Aromatase and breast cancer". Front. Biosci. 3: d922–33. PMID 9696881.  
  • Strobel HW, Thompson CM, Antonovic L (2001). "Cytochromes P450 in brain: function and significance". Curr. Drug Metab. 2 (2): 199–214. doi:10.2174/1389200013338577. PMID 11469726.  
  • Simpson ER, Clyne C, Rubin G, et al. (2002). "Aromatase--a brief overview". Annu. Rev. Physiol. 64: 93–127. doi:10.1146/annurev.physiol.64.081601.142703. PMID 11826265.  
  • Bulun SE, Yang S, Fang Z, et al. (2002). "Role of aromatase in endometrial disease". J. Steroid Biochem. Mol. Biol. 79 (1-5): 19–25. doi:10.1016/S0960-0760(01)00134-0. PMID 11850203.  
  • Balthazart J, Baillien M, Ball GF (2002). "Phosphorylation processes mediate rapid changes of brain aromatase activity". J. Steroid Biochem. Mol. Biol. 79 (1-5): 261–77. doi:10.1016/S0960-0760(01)00143-1. PMID 11850233.  
  • Richards JA, Petrel TA, Brueggemeier RW (2002). "Signaling pathways regulating aromatase and cyclooxygenases in normal and malignant breast cells". J. Steroid Biochem. Mol. Biol. 80 (2): 203–12. doi:10.1016/S0960-0760(01)00187-X. PMID 11897504.  
  • Balthazart J, Baillien M, Ball GF (2002). "Interactions between aromatase (estrogen synthase) and dopamine in the control of male sexual behavior in quail". Comp. Biochem. Physiol. B, Biochem. Mol. Biol. 132 (1): 37–55. doi:10.1016/S1096-4959(01)00531-0. PMID 11997208.  
  • Meinhardt U, Mullis PE (2002). "The aromatase cytochrome P-450 and its clinical impact". Horm. Res. 57 (5-6): 145–52. doi:10.1159/000058374. PMID 12053085.  
  • Carreau S, Bourguiba S, Lambard S, et al. (2003). "Reproductive system: aromatase and estrogens". Mol. Cell. Endocrinol. 193 (1-2): 137–43. doi:10.1016/S0303-7207(02)00107-7. PMID 12161013.  
  • Meinhardt U, Mullis PE (2003). "The essential role of the aromatase/p450arom". Semin. Reprod. Med. 20 (3): 277–84. doi:10.1055/s-2002-35374. PMID 12428207.  
  • Carreau S, Bourguiba S, Lambard S, Galeraud-Denis I (2003). "[Testicular aromatase]". J. Soc. Biol. 196 (3): 241–4. PMID 12462076.  
  • Carani C, Fabbi M, Zirilli L, Sgarbi I (2003). "[Estrogen resistance and aromatase deficiency in humans]". J. Soc. Biol. 196 (3): 245–8. PMID 12462077.  
  • Kragie L (2003). "Aromatase in primate pregnancy: a review". Endocr. Res. 28 (3): 121–8. doi:10.1081/ERC-120015041. PMID 12489562.  
  • Simpson ER (2004). "Biology of aromatase in the mammary gland". Journal of mammary gland biology and neoplasia 5 (3): 251–8. doi:10.1023/A:1009590626450. PMID 14973387.  
  • Bulun SE, Takayama K, Suzuki T, et al. (2004). "Organization of the human aromatase p450 (CYP19) gene". Semin. Reprod. Med. 22 (1): 5–9. doi:10.1055/s-2004-823022. PMID 15083376.  
  • Simpson ER (2004). "Aromatase: biologic relevance of tissue-specific expression". Semin. Reprod. Med. 22 (1): 11–23. doi:10.1055/s-2004-823023. PMID 15083377.  
  • Bulun SE, Fang Z, Imir G, et al. (2004). "Aromatase and endometriosis". Semin. Reprod. Med. 22 (1): 45–50. doi:10.1055/s-2004-823026. PMID 15083380.  
  • Shozu M, Murakami K, Inoue M (2004). "Aromatase and leiomyoma of the uterus". Semin. Reprod. Med. 22 (1): 51–60. doi:10.1055/s-2004-823027. PMID 15083381.  
  • Chen S, Ye J, Kijima I, et al. (2005). "Positive and negative transcriptional regulation of aromatase expression in human breast cancer tissue". J. Steroid Biochem. Mol. Biol. 95 (1-5): 17–23. doi:10.1016/j.jsbmb.2005.04.002. PMID 15955695.  
  • Lambard S, Silandre D, Delalande C, et al. (2005). "Aromatase in testis: expression and role in male reproduction". J. Steroid Biochem. Mol. Biol. 95 (1-5): 63–9. doi:10.1016/j.jsbmb.2005.04.020. PMID 16019206.  
  • Bulun SE, Imir G, Utsunomiya H, et al. (2005). "Aromatase in endometriosis and uterine leiomyomata". J. Steroid Biochem. Mol. Biol. 95 (1-5): 57–62. doi:10.1016/j.jsbmb.2005.04.012. PMID 16024248.  
  • Lambard S, Carreau S (2005). "Aromatase and oestrogens in human male germ cells". Int. J. Androl. 28 (5): 254–9. doi:10.1111/j.1365-2605.2005.00546.x. PMID 16128984.  
  • Ellem SJ, Risbridger GP (2006). "Aromatase and prostate cancer". Minerva Endocrinol. 31 (1): 1–12. PMID 16498360.  
  • Brueggemeier RW, Díaz-Cruz ES (2006). "Relationship between aromatase and cyclooxygenases in breast cancer: potential for new therapeutic approaches". Minerva Endocrinol. 31 (1): 13–26. PMID 16498361.  
  • Jongen VH, Hollema H, Van Der Zee AG, Heineman MJ (2006). "Aromatase in the context of breast and endometrial cancer. A review". Minerva Endocrinol. 31 (1): 47–60. PMID 16498363.  
  • Hiltunen M, Iivonen S, Soininen H (2006). "Aromatase enzyme and Alzheimer's disease". Minerva Endocrinol. 31 (1): 61–73. PMID 16498364.  

External links


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