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Gene Review

Cyp19a1  -  cytochrome P450, family 19, subfamily a,...

Mus musculus

Synonyms: Ar, ArKO, Arom, Aromatase, CYPXIX, ...
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Disease relevance of Cyp19a1

  • By 1 year of age, there is B cell hyperplasia in the bone marrow, spleen, and blood of ArKO mice and spontaneous autoimmune manifestations such as proteinuria and severe leukocyte infiltration in the salivary glands and kidney [1].
  • Male mice deficient in aromatase were initially fertile but developed progressive infertility, until their ability to sire pups was severely impaired [2].
  • Breast tumors, however, secrete soluble factors that stimulate aromatase expression through an alternative proximal promoter, promoter II [3].
  • We have shown previously, that ArKO mice present with age-progressive obesity and hepatic steatosis, and by 1 yr of age both male and female ArKO mice develop hypercholesterolemia [4].
  • We have reported that aromatase-knockout (ArKO) mice showed bone loss by increased bone resorption not only in female but also in male mice, suggesting essential roles of estrogen in bone metabolism in both sexes [5].

Psychiatry related information on Cyp19a1

  • The results indicate that despite the pronounced redistribution of sleep and motor activity in oestrogen deficient mice, the basic homeostatic mechanisms of sleep regulation in ArKO mice remain intact [6].
  • Attraction thresholds and sex discrimination of urinary odorants in male and female aromatase knockout (ArKO) mice [7].
  • Overall, we found that aromatase activity and P(4) levels change in association with an important life history transition, and may provide a mechanistic basis for plasticity in paternal behavior [8].

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


Regulatory relationships of Cyp19a1


Other interactions of Cyp19a1

  • To address this question, we have used mice that were rendered estradiol-deficient or estradiol-resistant by targeted disruption of aromatase (ArKO) or ERalpha (alphaERKO) respectively [19].
  • Upon treatment of ArKO mice with the ERbeta agonist 2,3-bis(4-hydroxyphenyl)propionitrile, GLUT4 expression was reduced [28].
  • As a result, betaERKO ovaries were unable to fully respond to an ovulatory bolus of gonadotropin, leading to a reduced rate of follicle rupture; insufficient induction of prostaglandin-synthase 2 and progesterone receptor; an aberrant increase in aromatase activity and plasma estradiol; and incomplete expansion of the cumulus-oocyte complex [29].
  • Cyp19 encodes the key enzyme of estrogen biosynthesis, aromatase cytochrome P450 [30].
  • In contrast, Cyp17 and Cyp19 expression were elevated in alphaERKO but normal in betaERKO and alphabetaERKO [31].

Analytical, diagnostic and therapeutic context of Cyp19a1


  1. Aromatase-deficient mice spontaneously develop a lymphoproliferative autoimmune disease resembling Sjogren's syndrome. Shim, G.J., Warner, M., Kim, H.J., Andersson, S., Liu, L., Ekman, J., Imamov, O., Jones, M.E., Simpson, E.R., Gustafsson, J.A. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  2. Impairment of spermatogenesis in mice lacking a functional aromatase (cyp 19) gene. Robertson, K.M., O'Donnell, L., Jones, M.E., Meachem, S.J., Boon, W.C., Fisher, C.R., Graves, K.H., McLachlan, R.I., Simpson, E.R. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  3. 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]
  4. The aromatase knockout mouse presents with a sexually dimorphic disruption to cholesterol homeostasis. Hewitt, K.N., Boon, W.C., Murata, Y., Jones, M.E., Simpson, E.R. Endocrinology (2003) [Pubmed]
  5. Estrogen and androgen play distinct roles in bone turnover in male mice before and after reaching sexual maturity. Matsumoto, C., Inada, M., Toda, K., Miyaura, C. Bone (2006) [Pubmed]
  6. Sleep and rest regulation in young and old oestrogen-deficient female mice. Vyazovskiy, V.V., Kopp, C., Wigger, E., Jones, M.E., Simpson, E.R., Tobler, I. J. Neuroendocrinol. (2006) [Pubmed]
  7. Attraction thresholds and sex discrimination of urinary odorants in male and female aromatase knockout (ArKO) mice. Pierman, S., Douhard, Q., Balthazart, J., Baum, M.J., Bakker, J. Hormones and behavior. (2006) [Pubmed]
  8. Variation in aromatase activity in the medial preoptic area and plasma progesterone is associated with the onset of paternal behavior. Trainor, B.C., Bird, I.M., Alday, N.A., Schlinger, B.A., Marler, C.A. Neuroendocrinology (2003) [Pubmed]
  9. Mechanisms of estrogen action. Nilsson, S., Mäkelä, S., Treuter, E., Tujague, M., Thomsen, J., Andersson, G., Enmark, E., Pettersson, K., Warner, M., Gustafsson, J.A. Physiol. Rev. (2001) [Pubmed]
  10. A fission yeast chromosome can replicate autonomously in mouse cells. Allshire, R.C., Cranston, G., Gosden, J.R., Maule, J.C., Hastie, N.D., Fantes, P.A. Cell (1987) [Pubmed]
  11. Estrogen and spermatogenesis. O'Donnell, L., Robertson, K.M., Jones, M.E., Simpson, E.R. Endocr. Rev. (2001) [Pubmed]
  12. Insulin-like growth factors as intraovarian regulators of granulosa cell growth and function. Adashi, E.Y., Resnick, C.E., D'Ercole, A.J., Svoboda, M.E., Van Wyk, J.J. Endocr. Rev. (1985) [Pubmed]
  13. Alpha-fetoprotein protects the developing female mouse brain from masculinization and defeminization by estrogens. Bakker, J., De Mees, C., Douhard, Q., Balthazart, J., Gabant, P., Szpirer, J., Szpirer, C. Nat. Neurosci. (2006) [Pubmed]
  14. Transient neonatal estrogen exposure to estrogen-deficient mice (aromatase knockout) reduces prostate weight and induces inflammation in late life. Bianco, J.J., McPherson, S.J., Wang, H., Prins, G.S., Risbridger, G.P. Am. J. Pathol. (2006) [Pubmed]
  15. Aromatase overexpression transgenic mice model: cell type specific expression and use of letrozole to abrogate mammary hyperplasia without affecting normal physiology. Mandava, U., Kirma, N., Tekmal, R.R. J. Steroid Biochem. Mol. Biol. (2001) [Pubmed]
  16. The aromatase inhibitor, 4-hydroxyandrostenedione, restores immune responses following trauma-hemorrhage in males and decreases mortality from subsequent sepsis. Schneider, C.P., Nickel, E.A., Samy, T.S., Schwacha, M.G., Cioffi, W.G., Bland, K.I., Chaudry, I.H. Shock (2000) [Pubmed]
  17. Effects of the antiestrogen tamoxifen and the aromatase inhibitor letrozole on serum hormones and bone characteristics in a preclinical tumor model for breast cancer. Núñez, N.P., Jelovac, D., Macedo, L., Berrigan, D., Perkins, S.N., Hursting, S.D., Barrett, J.C., Brodie, A. Clin. Cancer Res. (2004) [Pubmed]
  18. Participation of mitogen-activated protein kinase in luteinizing hormone-induced differential regulation of steroidogenesis and steroidogenic gene expression in mural and cumulus granulosa cells of mouse preovulatory follicles. Su, Y.Q., Nyegaard, M., Overgaard, M.T., Qiao, J., Giudice, L.C. Biol. Reprod. (2006) [Pubmed]
  19. Estrogens protect pancreatic beta-cells from apoptosis and prevent insulin-deficient diabetes mellitus in mice. Le May, C., Chu, K., Hu, M., Ortega, C.S., Simpson, E.R., Korach, K.S., Tsai, M.J., Mauvais-Jarvis, F. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  20. Relative impact of androgen and estrogen receptor activation in the effects of androgens on trabecular and cortical bone in growing male mice: a study in the androgen receptor knockout mouse model. Venken, K., De Gendt, K., Boonen, S., Ophoff, J., Bouillon, R., Swinnen, J.V., Verhoeven, G., Vanderschueren, D. J. Bone Miner. Res. (2006) [Pubmed]
  21. Gene expression profiles of cumulus cell oocyte complexes during ovulation reveal cumulus cells express neuronal and immune-related genes: does this expand their role in the ovulation process? Hernandez-Gonzalez, I., Gonzalez-Robayna, I., Shimada, M., Wayne, C.M., Ochsner, S.A., White, L., Richards, J.S. Mol. Endocrinol. (2006) [Pubmed]
  22. Characterization of mice deficient in aromatase (ArKO) because of targeted disruption of the cyp19 gene. Fisher, C.R., Graves, K.H., Parlow, A.F., Simpson, E.R. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  23. A steroidogenic factor-1-binding site and cyclic adenosine 3',5'-monophosphate response element-like elements are required for the activity of the rat aromatase promoter in rat Leydig tumor cell lines. Young, M., McPhaul, M.J. Endocrinology (1998) [Pubmed]
  24. Aminoglutethimide, a steroidogenesis inhibitor, abolishes hormonal induction of ornithine decarboxylase in steroidogenic tissues: evidence for its role as cAMP-dependent protein kinase inhibitor. Bastida, C.M., Tejada, F., Cremades, A., Peñafiel, R. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  25. Estrogen receptor alpha is required for mammary development and the induction of mammary hyperplasia and epigenetic alterations in the aromatase transgenic mice. Tekmal, R.R., Liu, Y.G., Nair, H.B., Jones, J., Perla, R.P., Lubahn, D.B., Korach, K.S., Kirma, N. J. Steroid Biochem. Mol. Biol. (2005) [Pubmed]
  26. Expression of the estrogen-inducible EGFP gene in aromatase-null mice reveals differential tissue responses to estrogenic compounds. Toda, K., Hayashi, Y., Okada, T., Morohashi, K., Saibara, T. Mol. Cell. Endocrinol. (2005) [Pubmed]
  27. Sex differences in the regulation of embryonic brain aromatase. Hutchison, J.B., Beyer, C., Hutchison, R.E., Wozniak, A. J. Steroid Biochem. Mol. Biol. (1997) [Pubmed]
  28. Muscle GLUT4 regulation by estrogen receptors ERbeta and ERalpha. Barros, R.P., Machado, U.F., Warner, M., Gustafsson, J.A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  29. Estrogen receptor-beta is critical to granulosa cell differentiation and the ovulatory response to gonadotropins. Couse, J.F., Yates, M.M., Deroo, B.J., Korach, K.S. Endocrinology (2005) [Pubmed]
  30. 0.2kb promoter sequence of the murine Cyp19 gene target beta-galactosidase expression to specific brain areas of transgenic mice. Nausch, N., Manteuffel, G., Vanselow, J. J. Steroid Biochem. Mol. Biol. (2007) [Pubmed]
  31. Characterization of the hypothalamic-pituitary-gonadal axis in estrogen receptor (ER) Null mice reveals hypergonadism and endocrine sex reversal in females lacking ERalpha but not ERbeta. Couse, J.F., Yates, M.M., Walker, V.R., Korach, K.S. Mol. Endocrinol. (2003) [Pubmed]
  32. Mammary gland development in transgenic male mice expressing human P450 aromatase. Li, X., Wärri, A., Mäkelä, S., Ahonen, T., Streng, T., Santti, R., Poutanen, M. Endocrinology (2002) [Pubmed]
  33. Individual differences in estrogen receptor alpha in select brain nuclei are associated with individual differences in aggression. Trainor, B.C., Greiwe, K.M., Nelson, R.J. Hormones and behavior. (2006) [Pubmed]
  34. Ontogenetic expression and sex differences of aromatase and estrogen receptor-alpha/beta mRNA in the mouse hippocampus. Ivanova, T., Beyer, C. Cell Tissue Res. (2000) [Pubmed]
  35. Dietary bisphenol A prevents ovarian degeneration and bone loss in female mice lacking the aromatase gene (Cyp19 ). Toda, K., Miyaura, C., Okada, T., Shizuta, Y. Eur. J. Biochem. (2002) [Pubmed]
  36. Targeted disruption of the aromatase P450 gene (Cyp19) in mice and their ovarian and uterine responses to 17beta-oestradiol. Toda, K., Takeda, K., Okada, T., Akira, S., Saibara, T., Kaname, T., Yamamura, K., Onishi, S., Shizuta, Y. J. Endocrinol. (2001) [Pubmed]
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