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Gene Review

CYP19A1  -  cytochrome P450, family 19, subfamily A,...

Homo sapiens

Synonyms: ARO, ARO1, Aromatase, CPV1, CYAR, ...
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Disease relevance of CYP19A1


Psychiatry related information on CYP19A1


High impact information on CYP19A1


Chemical compound and disease context of CYP19A1


Biological context of CYP19A1


Anatomical context of CYP19A1


Associations of CYP19A1 with chemical compounds


Physical interactions of CYP19A1

  • Additionally, beta-catenin is present in transcription complexes assembled on the endogenous gonad-specific CYP19A1 promoter, as evidenced by chromatin immunoprecipitation assays [23].
  • These findings suggest that treatments targeted at growth factor signalling pathways may be useful in patients acquiring resistance to oestrogen deprivation with aromatase inhibitors and that the pure anti-oestrogen ICI 182,780 may also be effective by blocking or destabilizing ER and hence disrupting cross-talk [28].
  • Stimulation of aromatase P450 promoter (II) activity in endometriosis and its inhibition in endometrium are regulated by competitive binding of steroidogenic factor-1 and chicken ovalbumin upstream promoter transcription factor to the same cis-acting element [29].
  • PGE2 increased GATA-4 binding to the Cyp19 promoter [30].
  • Experiments carried out with different models including turtles, crocodilians and lizards have demonstrated the implication of estrogens and the key role played by aromatase (the enzyme complex that converts androgens to estrogens) in ovary differentiation during TSP and in maintenance of the ovarian structure after TSP [31].

Enzymatic interactions of CYP19A1

  • Aromatase and cholesterol side-chain cleaving P450 mRNAs, proteins, and activities are measurable in human placentas and do not seem to be affected by maternal cigarette smoking [32].
  • In human placenta the enzyme complex aromatase catalyzes the conversion of androgens to estrogens and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) mediates the reversible interconversion of, e.g. estrone to estradiol [33].

Regulatory relationships of CYP19A1


Other interactions of CYP19A1

  • In the second trimester, increased O(2) tension promotes proteasomal degradation of USF1/2, resulting in syncytiotrophoblast differentiation and induction of hCYP19 expression [3].
  • Overexpression of Mash-2 prevents syncytiotrophoblast differentiation and induction of CYP19 expression [39].
  • The aromatase activity in the ER alpha-transfected SK-BR-3 cells could also be induced by environmental chemicals that were known to have an estrogen-like activity [4].
  • The aromatase C/C genotype together with a longer AR was also more frequent among controls (55%) than cases (41%; age- and BMI-adjusted OR, 0.51; 95% CI, 0.30-0.89) [40].
  • These results were consistent with enzyme activity data, suggesting that the effect of COX inhibitors on aromatase begins at the transcriptional level [34].
  • In endometrial stromal cells and the human endometrial surface epithelial (HES) cell line, induction of aromatase mRNA by A4 was associated with increased expression of SF-1 [41].

Analytical, diagnostic and therapeutic context of CYP19A1


  1. Profiling genetic variation along the androgen biosynthesis and metabolism pathways implicates several single nucleotide polymorphisms and their combinations as prostate cancer risk factors. Mononen, N., Seppälä, E.H., Duggal, P., Autio, V., Ikonen, T., Ellonen, P., Saharinen, J., Saarela, J., Vihinen, M., Tammela, T.L., Kallioniemi, O., Bailey-Wilson, J.E., Schleutker, J. Cancer Res. (2006) [Pubmed]
  2. Variants in Estrogen Biosynthesis Genes, Sex Steroid Hormone Levels, and Endometrial Cancer: A HuGE Review. Olson, S.H., Bandera, E.V., Orlow, I. Am. J. Epidemiol. (2007) [Pubmed]
  3. O2 enhancement of human trophoblast differentiation and hCYP19 (aromatase) gene expression are mediated by proteasomal degradation of USF1 and USF2. Jiang, B., Mendelson, C.R. Mol. Cell. Biol. (2005) [Pubmed]
  4. Induction of aromatase (CYP19) expression in breast cancer cells through a nongenomic action of estrogen receptor alpha. Kinoshita, Y., Chen, S. Cancer Res. (2003) [Pubmed]
  5. Induction of aromatase expression in cervical carcinomas: effects of endogenous estrogen on cervical cancer cell proliferation. Nair, H.B., Luthra, R., Kirma, N., Liu, Y.G., Flowers, L., Evans, D., Tekmal, R.R. Cancer Res. (2005) [Pubmed]
  6. CCAAT/enhancer binding protein beta regulates aromatase expression via multiple and novel cis-regulatory sequences in uterine leiomyoma. Ishikawa, H., Fenkci, V., Fencki, V., Marsh, E.E., Yin, P., Chen, D., Cheng, Y.H., Reisterd, S., Lin, Z., Bulun, S.E. J. Clin. Endocrinol. Metab. (2008) [Pubmed]
  7. Progesterone receptor inhibits aromatase and inflammatory response pathways in breast cancer cells via ligand-dependent and ligand-independent mechanisms. Hardy, D.B., Janowski, B.A., Chen, C.C., Mendelson, C.R. Mol. Endocrinol. (2008) [Pubmed]
  8. Diminished aromatase immunoreactivity in the hypothalamus, but not in the basal forebrain nuclei in Alzheimer's disease. Ishunina, T.A., van Beurden, D., van der Meulen, G., Unmehopa, U.A., Hol, E.M., Huitinga, I., Swaab, D.F. Neurobiol. Aging (2005) [Pubmed]
  9. Estrogen: consequences and implications of human mutations in synthesis and action. Grumbach, M.M., Auchus, R.J. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  10. Sex steroid-related genes and male-to-female transsexualism. Henningsson, S., Westberg, L., Nilsson, S., Lundström, B., Ekselius, L., Bodlund, O., Lindström, E., Hellstrand, M., Rosmond, R., Eriksson, E., Landén, M. Psychoneuroendocrinology (2005) [Pubmed]
  11. A candidate gene study of CYP19 (aromatase) and male sexual orientation. DuPree, M.G., Mustanski, B.S., Bocklandt, S., Nievergelt, C., Hamer, D.H. Behav. Genet. (2004) [Pubmed]
  12. Genetic polymorphisms of cytochrome P450 19 and 1B1, alcohol use, and breast cancer risk in Korean women. Lee, K.M., Abel, J., Ko, Y., Harth, V., Park, W.Y., Seo, J.S., Yoo, K.Y., Choi, J.Y., Shin, A., Ahn, S.H., Noh, D.Y., Hirvonen, A., Kang, D. Br. J. Cancer (2003) [Pubmed]
  13. Aromatase inhibitors as adjuvant therapy for postmenopausal patients with early stage breast cancer. Kudachadkar, R., O'Regan, R.M. CA: a cancer journal for clinicians. (2005) [Pubmed]
  14. Loci on chromosomes 2 (NIDDM1) and 15 interact to increase susceptibility to diabetes in Mexican Americans. Cox, N.J., Frigge, M., Nicolae, D.L., Concannon, P., Hanis, C.L., Bell, G.I., Kong, A. Nat. Genet. (1999) [Pubmed]
  15. Increased bone mass as a result of estrogen therapy in a man with aromatase deficiency. Bilezikian, J.P., Morishima, A., Bell, J., Grumbach, M.M. N. Engl. J. Med. (1998) [Pubmed]
  16. Effect of testosterone and estradiol in a man with aromatase deficiency. Carani, C., Qin, K., Simoni, M., Faustini-Fustini, M., Serpente, S., Boyd, J., Korach, K.S., Simpson, E.R. N. Engl. J. Med. (1997) [Pubmed]
  17. An aromatase-producing sex-cord tumor resulting in prepubertal gynecomastia. Coen, P., Kulin, H., Ballantine, T., Zaino, R., Frauenhoffer, E., Boal, D., Inkster, S., Brodie, A., Santen, R. N. Engl. J. Med. (1991) [Pubmed]
  18. Tumor-stromal interaction through the estrogen-signaling pathway in human breast cancer. Yamaguchi, Y., Takei, H., Suemasu, K., Kobayashi, Y., Kurosumi, M., Harada, N., Hayashi, S. Cancer Res. (2005) [Pubmed]
  19. Biochemical and biological characterization of a novel anti-aromatase coumarin derivative. Chen, S., Cho, M., Karlsberg, K., Zhou, D., Yuan, Y.C. J. Biol. Chem. (2004) [Pubmed]
  20. High expression of steroid sulfatase mRNA predicts poor prognosis in patients with estrogen receptor-positive breast cancer. Miyoshi, Y., Ando, A., Hasegawa, S., Ishitobi, M., Taguchi, T., Tamaki, Y., Noguchi, S. Clin. Cancer Res. (2003) [Pubmed]
  21. A single-nucleotide polymorphism in the aromatase gene is associated with the efficacy of the aromatase inhibitor letrozole in advanced breast carcinoma. Colomer, R., Monzo, M., Tusquets, I., Rifa, J., Baena, J.M., Barnadas, A., Calvo, L., Carabantes, F., Crespo, C., Muñoz, M., Llombart, A., Plazaola, A., Artells, R., Gilabert, M., Lloveras, B., Alba, E. Clin. Cancer Res. (2008) [Pubmed]
  22. Variation in estrogen-related genes and cross-sectional and longitudinal blood pressure in the Framingham Heart Study. Peter, I., Shearman, A.M., Zucker, D.R., Schmid, C.H., Demissie, S., Cupples, L.A., Larson, M.G., Vasan, R.S., D'Agostino, R.B., Karas, R.H., Mendelsohn, M.E., Housman, D.E., Levy, D. J. Hypertens. (2005) [Pubmed]
  23. Follicle-stimulating hormone/cAMP regulation of aromatase gene expression requires beta-catenin. Parakh, T.N., Hernandez, J.A., Grammer, J.C., Weck, J., Hunzicker-Dunn, M., Zeleznik, A.J., Nilson, J.H. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  24. Testosterone attenuates expression of vascular cell adhesion molecule-1 by conversion to estradiol by aromatase in endothelial cells: implications in atherosclerosis. Mukherjee, T.K., Dinh, H., Chaudhuri, G., Nathan, L. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  25. Liver receptor homologue-1 (LRH-1) regulates expression of aromatase in preadipocytes. Clyne, C.D., Speed, C.J., Zhou, J., Simpson, E.R. J. Biol. Chem. (2002) [Pubmed]
  26. Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome. Frasor, J., Chang, E.C., Komm, B., Lin, C.Y., Vega, V.B., Liu, E.T., Miller, L.D., Smeds, J., Bergh, J., Katzenellenbogen, B.S. Cancer Res. (2006) [Pubmed]
  27. The role of growth factor receptor pathways in human breast cancer cells adapted to long-term estrogen deprivation. Sabnis, G.J., Jelovac, D., Long, B., Brodie, A. Cancer Res. (2005) [Pubmed]
  28. Elevated ERK1/ERK2/estrogen receptor cross-talk enhances estrogen-mediated signaling during long-term estrogen deprivation. Martin, L.A., Farmer, I., Johnston, S.R., Ali, S., Dowsett, M. Endocr. Relat. Cancer (2005) [Pubmed]
  29. Stimulation of aromatase P450 promoter (II) activity in endometriosis and its inhibition in endometrium are regulated by competitive binding of steroidogenic factor-1 and chicken ovalbumin upstream promoter transcription factor to the same cis-acting element. Zeitoun, K., Takayama, K., Michael, M.D., Bulun, S.E. Mol. Endocrinol. (1999) [Pubmed]
  30. Prostaglandin E2 increases cyp19 expression in rat granulosa cells: Implication of GATA-4. Cai, Z., Kwintkiewicz, J., Young, M.E., Stocco, C. Mol. Cell. Endocrinol. (2007) [Pubmed]
  31. Temperature-dependent sex determination and gonadal differentiation in reptiles. Pieau, C., Dorizzi, M., Richard-Mercier, N. EXS. (2001) [Pubmed]
  32. The expression and environmental regulation of P450 enzymes in human placenta. Pasanen, M., Pelkonen, O. Crit. Rev. Toxicol. (1994) [Pubmed]
  33. Regulation of aromatase cytochrome P-450 and 17 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid levels in choriocarcinoma cells. Ritvos, O., Voutilainen, R. Endocrinology (1992) [Pubmed]
  34. Cyclooxygenase inhibitors suppress aromatase expression and activity in breast cancer cells. Díaz-Cruz, E.S., Shapiro, C.L., Brueggemeier, R.W. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  35. Cyclooxygenase-2 directly regulates gene expression of P450 Cyp19 aromatase promoter regions pII, pI.3 and pI.7 and estradiol production in human breast tumor cells. Prosperi, J.R., Robertson, F.M. Prostaglandins Other Lipid Mediat. (2006) [Pubmed]
  36. Novel sulfonanilide analogues suppress aromatase expression and activity in breast cancer cells independent of COX-2 inhibition. Su, B., Diaz-Cruz, E.S., Landini, S., Brueggemeier, R.W. J. Med. Chem. (2006) [Pubmed]
  37. Aromatase expression in endometriosis. Noble, L.S., Simpson, E.R., Johns, A., Bulun, S.E. J. Clin. Endocrinol. Metab. (1996) [Pubmed]
  38. Ad4BP/SF-1 regulates cyclic AMP-induced transcription from the proximal promoter (PII) of the human aromatase P450 (CYP19) gene in the ovary. Michael, M.D., Kilgore, M.W., Morohashi, K., Simpson, E.R. J. Biol. Chem. (1995) [Pubmed]
  39. USF1 and USF2 mediate inhibition of human trophoblast differentiation and CYP19 gene expression by Mash-2 and hypoxia. Jiang, B., Mendelson, C.R. Mol. Cell. Biol. (2003) [Pubmed]
  40. Allelic variants of aromatase and the androgen and estrogen receptors: toward a multigenic model of prostate cancer risk. Modugno, F., Weissfeld, J.L., Trump, D.L., Zmuda, J.M., Shea, P., Cauley, J.A., Ferrell, R.E. Clin. Cancer Res. (2001) [Pubmed]
  41. Androstenedione up-regulation of endometrial aromatase expression via local conversion to estrogen: potential relevance to the pathogenesis of endometriosis. Bukulmez, O., Hardy, D.B., Carr, B.R., Auchus, R.J., Toloubeydokhti, T., Word, R.A., Mendelson, C.R. J. Clin. Endocrinol. Metab. (2008) [Pubmed]
  42. Spatially heterogeneous expression of aromatase P450 through promoter II is closely correlated with the level of steroidogenic factor-1 transcript in endometrioma tissues. Yang, H.J., Shozu, M., Murakami, K., Sumitani, H., Segawa, T., Kasai, T., Inoue, M. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  43. Aromatase and 17 beta-hydroxysteroid dehydrogenase type 1 in human breast carcinoma. Sasano, H., Frost, A.R., Saitoh, R., Harada, N., Poutanen, M., Vihko, R., Bulun, S.E., Silverberg, S.G., Nagura, H. J. Clin. Endocrinol. Metab. (1996) [Pubmed]
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