Aromatase research and its clinical significance

Endokrynologia Polska

Volumn 61, Issue 1, 2010, Pages 126-134

  Czajka Oraniec, Izabella ^a   Simpson, Evan R ^b  

^a Department of Endocrinology   (United States)

^b HUDSON INSTITUTE OF MEDICAL RESEARCH   (Australia)

Author keywords

Aaromatase; Androgens; Aromatase inhibitors; Breast cancer; Oestrogens

Indexed keywords

AMINOGLUTETHIMIDE; ANASTROZOLE; ANDROGEN; AROMATASE; DEXAMETHASONE; ESTROGEN; HYDROCORTISONE; LETROZOLE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; TAMOXIFEN;

BIOSYNTHESIS; BONE METABOLISM; BREAST CANCER; CANCER RESISTANCE; CHROMOSOME 15; CLINICAL TRIAL; DRUG EFFICACY; DRUG INHIBITION; DRUG POTENCY; DRUG SAFETY; DRUG SPECIFICITY; ENDOMETRIUM CANCER; ESTROGEN DEFICIENCY; GENE EXPRESSION; GENETIC POLYMORPHISM; HUMAN; HYPOPHYSECTOMY; IMMUNOHISTOCHEMISTRY; NONHUMAN; PREMENOPAUSE; PROTEIN DEFICIENCY; REVIEW; STEROIDOGENESIS;

ANIMALS; AROMATASE; AROMATASE INHIBITORS; BONE AND BONES; BREAST NEOPLASMS; ESTROGENS; FEMALE; HUMANS; MALE; MICE; POLYMORPHISM, GENETIC;

EID: 77950545912     PISSN: 0423104X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (129)

1. Miller WL. Minireview: Regulation of steroidogenesis by electron transfer. Endocrinology 2005; 146: 2544-2550.
2. Simpson ER, Mahendroo MS, Means GD et al. Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev 1994; 15: 342-355.
3. Mendelson CR, Wright EE, Evans CT et al. Preparation and characterization of polyclonal and monoclonal antibodies against human aromatase cytochrome P-450 (P-450AROM), and their use in its purification. Arch Biochem Biophys 1985; 243: 480-491.
4. Kellis JT, Jr., Vickery LE. Purification and characterization of human placental aromatase cytochrome P-450. J Biol Chem 1987; 262: 4413-4420. (Pubitemid 17102645)
5. Osawa Y, Yoshida N, Fronckowiak M et al. Immunoaffinity purification of aromatase cytochrome P-450 from human placental microsomes, metabolc switching from aromatization to 1 beta and 2 beta-monohydroxylation, and recognition of aromatase isozymes. Steroids 1987; 50: 11-28.
6. Hall PF, Chen S, Nakajin S et al. Purification and characterization of aromatase from human placenta. Steroids 1987; 50: 37-50.
7. Conley A, Hinshelwood M. Mammalian aromatases. Reproduction 2001; 121: 685-695. (Pubitemid 32472054)
8. Payne AH, Hales DB. Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones. Endocr Rev 2004; 25: 947-970. (Pubitemid 39657774)
9. Simpson ER, Clyne C, Rubin G et al. Aromatase - a brief overview. Annu Rev Physiol 2002; 64: 93-127. (Pubitemid 34259227)
10. Means GD, Kilgore MW, Mahendroo MS et al. Tissue-specific promoters regulate aromatase cytochrome P450 gene expression in human ovary and fetal tissues. Mol Endocrinol 1991; 5: 2005-2013.
11. Mahendroo MS, Means GD, Mendelson CR, Simpson ER. Tissue-specific expression of human P-450AROM. The promoter responsible for expression in adipose tissue is different from that utilized in placenta. J Biol Chem 1991; 266: 11276-11281.
12. Carreau S, Bourguiba S, Lambard S et al. The promoter(s) of the aromatase gene in male testicular cells. Reproductive Oncology 2004; 4: 23-34.
13. Balthazart J, Baillien M, Charlier TD et al. Multiple mechanisms control brain aromatase activity at the genomic and non-genomic level. J Steroid Biochem Mol Biol 2003; 86: 367-379. (Pubitemid 37420004)
14. Clyne CD, Speed CJ, Zhou J et al. Liver receptor homologue-1 (LRH-1) regulates expression of aromatase in preadipocytes. J Biol Chem 2002; 277: 20591-20597. (Pubitemid 34967360)
15. Harada N. A unique aromatase (P450) mRNA formed by alternative use of tissue specific exons I in human skin fibroblasts. Biochem Biophys Res Commun 1992; 189: 1001-1007. (Pubitemid 23032474)
16. Harada N, Sasano H, Murakami H et al. Localized expression of aromatase in human vascular tissues. Circ Res 1999; 84: 1285-1291. (Pubitemid 29270043)
17. Oz OK, Millsaps R, Welch R et al. Expression of aromatase in the human growth plate. J Mol Endocrinol 2001; 27: 249-253. (Pubitemid 32970691)
18. Nawata H, Tanaka S, Tanaka S et al. Aromatase in bone cells: association with osteoporosis in postmenopausal women. J Steroid Biochem Mol Biol 1995; 53: 165-174.
19. Simpson ER. Sources of estrogen and their importance. J Steroid Biochem Mol Biol 2003; 86: 225-230.
20. Braunstein GD. Aromatase and gynecomastia. Endocr Relat Cancer 1999; 6: 315-324
21. Yue W, Wang JP, Hamilton CJ et al. In situ aromatization enhances breast tumor estradiol levels and cellular proliferation. Cancer Res 1998; 58: 927-932. (Pubitemid 28182460)
22. Means GD, Mahendroo MS, Corbin CJ et al. Structural analysis of the gene encoding human aromatase cytochrome P-450, the enzyme responsible for estrogen biosynthesis. J Biol Chem 1989; 264: 19385-19391.
23. Harada N, Yamada K, Saito K et al. Structural characterization of the human estrogen synthetase (aromatase) gene. Biochem Biophys Res Commun 1990; 166: 365-372. (Pubitemid 20040195)
24. Simpson ER, Michael MD, Agarwal VR et al. Expression of the CYP19 (aromatase) gene: an unusual case of alternative promoter usage. FA- SEB J 1997; 11: 29-36. (Pubitemid 27076321)
25. Sebastan S, Bulun SE. A highly complex organization of the regulatory region of the human CYP19 (aromatase) gene revealed by the Human genome project. J Clin Endocrinol Metab 2001; 86: 4600-4602.
26. Shozu M, Zhao Y, Bulun SE et al. Multiple splicing events involved in regulation of human aromatase expression by a novel promoter, 1.6. Endocrinology 1998; 139: 1610-1617. (Pubitemid 28513816)
27. Honda S, Harada N, Takagi Y. Novel exon 1 of the aromatase gene specific for aromatase transcripts in human brain. Biochemical & Biophysical Research Communications 1994; 198: 1153-1160. (Pubitemid 24172817)
28. Sebastian S, Takayama K, Shozu M et al. Cloning and characterization of a novel endothelial promoter of the human CYP19 (aromatase P450) gene that is up-regulated in breast cancer tissue. Mol Endocrinol 2002; 16: 2243-2254. (Pubitemid 35155537)
29. Utsumi T, Harada N, Maruta M et al. Presence of alternatively spliced transcripts of aromatase gene in human breast cancer. J Clin Endocrinol Metab 1996; 81: 2344-2349. (Pubitemid 26175966)
30. Agarwal VR, Bulun SE, Leitch M et al. Use of alternative promoters to express the aromatase cytochrome P450 (CYP19) gene in breast adipose tissues of cancer-free and breast cancer patients. Journal of Clinical Endocrinology & Metabolism 1996; 81: 3843-3849. (Pubitemid 26380384)
31. Harris RE, Namboodiri KK, Farrar WB. Nonsteroidal antiinflammatory drugs and breast cancer. Epidemiology 1996; 7: 203-205. (Pubitemid 26068056)
32. Irahara N, Miyoshi Y, Taguchi T et al. Possible involvement of aromatase overexpression induced by cyclo-oxygenase-2 in the pathogenesis of idiopathic gynecomastia. Endocr Res 2005; 31: 219-227. (Pubitemid 41769965)
33. Shozu M, Akasofu K, Harada T et al. A new cause of female pseudohermaphroditism: placental aromatase deficiency. J Clin Endocrinol Metab 1991; 72: 560-566. (Pubitemid 21921732)
34. Harada N, Ogawa H, Shozu M et al. Biochemical and molecular genetic analyses on placental aromatase (P450) deficiency. J Biol Chem 1992; 267: 4781-4785.
35. Ito Y, Fisher CR, Conte FA et al. Molecular basis of aromatase deficiency in an adult female with sexual infantilism and polycystic ovaries. Proc Natl Acad Sci USA. 1993; 90: 11673-21177 (Pubitemid 24008701)
36. Conte FA, Grumbach MM, Ito Y et al. A syndrome of female pseudo-hermaphrodism, hypergonadotropic hypogonadism, and multicystic ovaries associated with missense mutations in the gene encoding aromatase (P450arom). J Clin Endocrinol Metab 1994; 78: 1287-1292. (Pubitemid 24180993)
37. Morishima A, Grumbach MM, Simpson ER et al. Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metab 1995; 80: 3689-3698.
38. Carani C, Qin K, Simoni M et al. Effect of testosterone and estradiol in a man with aromatase deficiency. New Eng J Med 1997; 337: 91-95. (Pubitemid 27284394)
39. Mullis PE, Yoshimura N, Kuhlmann B et al. Aromatase deficiency in a female who is compound heterozygote for two new point mutations in the P450arom gene: impact of estrogens on hypergonadotropic hypogonadism, multicystic ovaries, and bone densitometry in childhood. J Clin Endocrinol Metab. 1997; 82: 1739-1745. (Pubitemid 127495177)
40. Deladoëy J, Flück C, Bex M et al. Aromatase deficiency caused by a novel P450arom gene mutation: impact of absent estrogen production on serum gonadotropin concentration in a boy. J Clin Endocrinol Metab. 1999; 84: 4050-4054. (Pubitemid 30644193)
41. Belgorosky A, Pepe C, Marino R et al. Hypothalamic-pituitary-ovarian axis during infancy, early and late prepuberty in an aromatase-deficient girl who is a compound heterocygote for two new point mutations of the CYP19 gene. J Clin Endocrinol Metab 2003; 88: 5127-5131. (Pubitemid 37452706)
42. Maffei L, Murata Y, Rochira V et al. Dysmetabolic syndrome in a man with a novel mutation of the aromatase gene: effects of testosterone, alendronate, and estradiol treatment. J Clin Endocrinol Metab 2004; 89: 61-70. (Pubitemid 38183860)
43. Mittre-Hervé MH, Kottler ML, Pura M. Human gene mutations. Gene symbol: CYP19. Disease: Aromatase deficiency. Hum Genet 2004; 114: 224.
44. Lin L, Ercan O, Raza J et al. Variable phenotypes associated with aromatase (CYP19) insufficiency in humans. J Clin Endocrinol Metab 2007; 92: 982-990. (Pubitemid 46465673)
45. Maffei L, Rochira V, Zirilli L et al. A novel compound heterozygous mutation of the aromatase gene in an adult man: reinforced evidence on the relationship between congenital oestrogen deficiency, adiposity and the metabolic syndrome. Clin Endocrinol (Oxf) 2007; 67: 218-224. (Pubitemid 47076295)
46. Lanfranco F, Zirilli L, Baldi M et al. A novel mutation in the human aromatase gene: insights on the relationship among serum estradiol, longitudinal growth and bone mineral density in an adult man under estrogen replacement treatment. Bone 2008; 43: 628-635.
47. Jones ME, Boon WC, Proietto J, Simpson ER. Of mice and men: the evolving phenotype of aromatase deficiency. Trends Endocrinol Metab 2006; 17: 55-64. (Pubitemid 43306728)
48. Fisher CR, Gra ves KH, Parlow AF, Simpson ER. Characterization of mice deficient in aromatase (ArKO) because of targeted disruption of the cypl9 gene. Proc Natl Acad Sci USA 1998; 95: 6965-6970.
49. Hewitt KN, Pratis K, Jones ME, Simpson ER. Estrogen replacement reverses the hepatic steatosis phenotype in the male aromatase knockout mouse 2004; 145: 1842-1848
50. Oz OK, Hirasawa G, Lawson J et al. Bone phenotype of the aromatase deficient mouse. J Steroid Biochem Mol Biol 2001; 79: 49-59. (Pubitemid 34158778)
51. Jones ME, Thorburn AW, Britt KL et al. Aroma tase-deficient (ArKO) mice accumulate excess adipose tissue. J Steroid Biochem Mol Biol 2001; 79: 3-9.
52. Takeda K, Toda K, Saibara T et al. Progressive development of insulin resistance phenotype in male mice with complete aromatase (CYP19) deficiency. J Endocrinol 2003; 176: 237-246. (Pubitemid 36284816)
53. Britt KL, Drummond AE, Dyson M et al. The ovarian phenotype of the aromatase knockout (ArKO) mouse. J Steroid Biochem Mol Biol 2001; 79: 181-185. (Pubitemid 34158793)
54. Robertson KM, O'Donnell L, Jones ME et al. Impairment of spermatogenesis in mice lacking a functional aromatase (cyp 19) gene. Proc Natl Acad Sci USA 1999; 96: 7986-7991. (Pubitemid 29328394)
55. Czajka-Oraniec IK, Chik C, Mitchell R et al. Long-term effects of estrogen deprivation in an aromatase deficient woman. Endocrine Society Annual Meeting ENDO, San Francisco, USA, 15-18 June 2008; Pl-610.
56. Rochira V, Zirilli L, Genazzani AD et al. Hypothalamic-pituitary-gona-dal axis in two men with aromatase deficiency: evidence that circulating estrogens are required at the hypothalamic level for the integrity of gonadotropin negative feedback. Eur J Endocrinol 2006; 155: 513-522. (Pubitemid 44608425)
57. Smith EP, Boyd J, Frank GR et al. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med 1994; 331: 1056-1061. (Pubitemid 24317698)
58. Rochira V, Madeo B, Zirilli L et al. Oestradiol replacement treatment and glucose homeostasis in two men with congenital aromatase deficiency: evidence for a role of oestradiol and sex steroids imbalance on insulin sensitivity in men. Diabet Med. 2007; 24: 1491-1495. (Pubitemid 350179451)
59. Li X, Warri A, Makela S, Ahonen T et al. Mammary gland development in transgenic male mice expressing human P450 aromatase. Endocrinology. 2002; 143: 4074-4083. (Pubitemid 35251782)
60. Gill K, Kirma N, Tekmal RR. Overexpression of aromatase in transgenic male mice results in the induction of gynecomastia and other biochemical changes in mammary glands. J Steroid Biochem Mol Biol 2001; 77: 13-18. (Pubitemid 32455349)
61. Luthra R, Kirma N, Jones J et al. Use of letrozole as a chemopreventive agent in aromatase overexpressing transgenic mice. J Steroid Biochem Mol Biol 2003; 86: 461-467. (Pubitemid 37412585)
62. 19-steroids. J Clin Invest 1985; 75: 1763-1769. (Pubitemid 15237783)
63. Leiberman E, Zachmann M. Familial adrenal feminization probably due to increased steroid aromatizabon. Horm Res 1992; 37: 96-102.
64. Stratakis CA, Vottero A, Brodie A et al. The aromatase excess syndrome is associated with feminization of both sexes and autosomal dominant transmission of aberrant P450 aromatase gene transcription. J Clin Endocrinol Metab 1998; 83: 1348-1357. (Pubitemid 28496419)
65. Shozu M, Sebastian S, Takayama K et al. Estrogen excess associated with novel gain-of-function mutations affecting the aromatase gene. N Engl J Med 2003; 348: 1855-1865. (Pubitemid 36532311)
66. Martin RM, Lin CJ, Nishi MY et al. Familial hyperestrogenism in both sexes: clinical, hormonal, and molecular studies of two siblings. J Clin Endocrinol Metab 2003; 88: 3027-3034.
67. Binder G, Iliev DI, Dufke A et al. Dominant transmission of prepubertal gynecomastia due to serum estrone excess: hormonal, biochemical, and genetic analysis in a large kindred. J Clin Endocrinol Metab 2005; 90: 484-492 (Pubitemid 40116698)
68. Demura M, Martin RM, Shozu M et al. Regional rearrangements in chromosome 15q21 cause formation of cryptic promoters for the CYP19 (aromatase) gene. Human Molecular Genetics 2007; 16: 2529-2541. (Pubitemid 47617720)
69. Bulun SE, Simpson ER. Regulation of aromatase expression in human tissues. Breast Cancer Res Treat 1994; 30: 19-29. (Pubitemid 24250756)
70. Cleland WH, Mendelson CR, Simpson ER. Effects of aging and obesity on aromatase activity of human adipose cells. J Clin Endocrinol Metab 1985; 60: 174-177.
71. Bulun SE, Simpson ER. Competitive RT-PCR analysis indicates levels of aromatase cytochrome P450 transcripts in adipose tissue of buttocks, thighs, and abdomen of women increase with advancing age. J Clin Endocrinol Metab 1994; 78: 428-432.
72. Southren AL, Olivo J, Gordon GG et al. The conversion of androgens to estrogens in hyperthyroidism. J Clin Endocrinol Metab 1974; 38: 207-214.
73. Bulard J, Mowszowicz I, Schaison G. Increased aromatase activity in pubic skin fibroblasts from patients with isolated gynecomastia. J Clin Endocrinol Metab 1987; 64: 618-623. (Pubitemid 17020933)
74. Coen P, Kulin H, Ballantine T et al. An aromatase-producing sex-cord tumor resulting in prepubertal gynecomastia. N Engl J Med 1991; 324: 334-335.
75. Duparc C, Boissiere-Veverka G, Lefebvre H et al. An oestrogen-producing seminoma responsible for gynecomastia. Horm Metab Res 2003; 35: 324-329.
76. Fukai N, Hirono Y, Yoshimoto T et al. A case of estrogen-secreting adrenocortical carcinoma with subclinical Cushing's Syndrome. Endocr J 2006; 53: 237-245.
77. Czajka I, Zgliczyński W, Kasperlik-Zaluska A et al. Gynecomastia as a first sign of adrenal carcinoma - case report. Endokrynol Pol 2005; 6: 926-930.
78. Agarwal VR, Takayama K, Van Wyk JJ et al. Molecular basis of severe gynecomastia associated with aromatase expression in a fibrolamellar hepatocellular carcinoma. J Clin Endocrinol Metab 1998; 83: 1797-1800. (Pubitemid 28501061)
79. Yaturu S, Harrara E, Nopajaroonsri C et al. Gynecomastia attributable to human chorionic gonadotropin-secreting giant cell carcinoma of lung. Endocr Pract 2003; 9: 233-235.
80. Santen RJ, Santner SJ, Harvey HA et al. Marked heterogeneity of aromatase activity in human malignant melanoma tissue. Eur J Cancer Clin Oncol 1988; 24: 1811-1816.
81. Ma CX, Adjei AA, Salavaggione OE et al. Human aromatase: gene resequencing and functional genomics. Cancer Res 2005; 65: 11071-11082. (Pubitemid 41713378)
82. Gennari L, Masi L, Merlotti D et al. A polymorphic CYP19 TTTA repeat influences aromatase activity and estrogen levels in elderly men: effects on bone metabolism. J Clin Endocr Metab 2004; 89: 2803-2810. (Pubitemid 38766369)
83. Dick IM, Devine A, Prince RL. Association of an aromatase TTTA repeat polymorphism with circulating estrogen, bone structure, and biochemistry in older women. Am J Physiol Endocrinol Metab 2005; 288: E989-E995. (Pubitemid 40547894)
84. Haiman CA, Hankinson SE, Spiegelman D et al. A tetranucleotide repeat polymorphism in CYP19 and breast cancer risk. Int J Cancer 2000; 87: 204-210. (Pubitemid 30434346)
85. Dunning AM, Dowsett M, Healey CS et al. Polymorphisms associated with circulating sex hormone levels in postmenopausal women. J Natl Cancer Inst 2004; 96: 936-945. (Pubitemid 38868140)
86. Kristensen VN, Harada N, Yoshimura N et al. Genetic variants of CYP19 (aromatase) and breast cancer risk. Oncogene 2000; 19: 1329-1333. (Pubitemid 30160625)
87. Baxter SW, Choong DY, Eccles DM et al. Polymorphic variation in CYP19 and the risk of breast cancer. Carcinogenesis 2001; 22: 347-349. (Pubitemid 32175526)
88. Probst-Hensch NM, Ingles SA, Diep AT et al. Aromatase and breast cancer susceptibility. Endocr Relat Cancer 1999; 6: 165-173.
89. Masi L, Becherini L, German L et al. Polymorphism of the aromatase gene in postmenopausal Italian women: distribution and correlation with bone mass and fracture risk. J Clin Endocrinol Metab 2001; 86: 2263-2269. (Pubitemid 32472950)
90. Berstein LM, Imyanitov EN, Kovalevskij AJ et al. CYP17 and CYP19 genetic polymorphisms in endometrial cancer: association with intratumoral aromatase activity. Cancer Lett 2004; 207: 191-196.
91. Paynter RA, Hankinson SE, Colditz GA et al. CYP19 (aromatase) haplotypes and endometrial cancer risk. Int J Cancer 2005; 116: 267-274. (Pubitemid 40967264)
92. Kado N, Kitawaki J, Obayashi H et al. Association of the CYP17 gene and CYP19 gene polymorphisms with risk of endometriosis in Japanese women. Hum Reprod 2002; 17: 897-902. (Pubitemid 34411118)
93. Arvanitis DA, Koumantakis GE, Goumenou AG et al. CYP1A1, CYP19, and GSTM1 polymorphisms increase the risk of endometriosis. Fertil Steril 2003; 79: 702-709.
94. Suzuki K, Nakazało H, Matsui H et al. Association of the genetic polymorphism of the CYP19 intron 4 [TTTA]n repeat with familial prostate cancer risk in a Japanese population. Anticancer Res 2003; 23: 4941-4946. (Pubitemid 38182108)
95. Tsuchiya N, Wang L, Suzuki H et al. Impact of IGF-I and CYP19 gene polymorphisms on the survival of patients with metastatic prostate cancer. J Clin Oncol 2006; 24: 1982-1989. (Pubitemid 46622105)
96. Czajka-Oraniec I, Zgliczynski W, Kurylowicz A et al. Association between gynecomastia and aromatase (CYP19) polymorphisms. Eur J Endocrinol 2008; 158: 721-727. (Pubitemid 351639611)
97. Beatson GT. On the treatment of inoperable cases of carcinoma of the mamma. Suggestions for a new method of treatment with illustrative cases. Lancet II 1896; 104-107.
98. Santen RJ, Manni A, Harvey H et al. Endocrine treatment of breast cancer in women. Endocrine Reviews 1990; 11: 221-265. (Pubitemid 20182870)
99. Tagnon HJ. Antiestrogens in treatment of breast cancer. Cancer 1977; (Suppl. 6): 2959-2964
100. Brueggemeier RW, Hackett JC, Diaz-Cruz ES. Aromatase inhibitors in the treatment of breast cancer. Endocr Rev 2005; 26: 331-345. (Pubitemid 40686647)
101. Lu Q, Nakmura J, Savinov A et al. Expression of aromatase protein and messenger ribonucleic acid in tumor epithelial cells and evidence of functional significance of locally produced estrogen in human breast cancers. Endocrinology 1996; 137: 3061-3068. (Pubitemid 26192205)
102. Miki Y, Suzuki T, Tazawa C et al. Aromatase localization in human breast cancer tissues: possible interactions between intratumoral stromal and parenchymal cells. Cancer Research 2007; 67: 3945-3954. (Pubitemid 46762184)
103. Santen RJ, Santner S, Davis B et al. Aminoglutethimide inhibits extra-glandular estrogen production in postmenopausal women with breast carcinoma. J Clin Endocrinol Metab 1978; 47: 1257-1265. (Pubitemid 9091287)
104. Cocconi G. First generation aromatase inhibitors-aminoglutethimide and testololactone. Breast Cancer Res Treat 1994; 30: 57-80. (Pubitemid 24250759)
105. Smith IE, Harris AL, Morgan M et al. Tamoxifen versus aminoglutethimide in advanced breast carcinoma: a randomized cross-over trial. Br Med J (Clin Res Ed) 1981; 283: 1432-1434. (Pubitemid 12229178)
106. Dowsett M, Coombes RC. Second generation aromatase inhibitor - 4-hydroxyandrostenedione. Breast Cancer Res Treat 1994; 30: 81-87. (Pubitemid 24250760)
107. Perez CR, Alberola C, V, Calabresi F et al. Comparison of the selective aromatase inhibitor formestane with tamoxifen as first-line hormonal therapy in postmenopausal women with advanced breast cancer. Ann Oncol 1994; 5 (Suppl. 24): S19-S24. (Pubitemid 24382828)
108. Steele RE, Mellor LB, Sawyer WK et al. In vitro and in vivo studies demonstrating potent and selective estrogen inhibition with the nonsteroidal aromatase inhibitor CGS16949A. Steroids 1987; 50: 147-161.
109. Trunet PF, Mueller P, Girard F et al. The effects of fadrozole hydrochloride on aldosterone secretion in healthy male subjects. J Clin Endocrinol Metab 1992; 74: 571-576.
110. Tominaga T, Adachi I, Sasaki Y et al. Double-blind randomised trial comparing the non-steroidal aromatase inhibitors letrozole and fadrozole in postmenopausal women with advanced breast cancer. Ann Oncol 2003; 14: 62-70.
111. Kleeberg UR, Dowsett M, Carrion RP et al. A randomised comparison of oestrogen suppression with anastrozole and formestane in postmenopausal patients with advanced breast cancer. Oncology 1997; 54 (Suppl. 2): 19-22. (Pubitemid 27466670)
112. Gershanovich M, Chaudri HA, Campos D et al. Letrozole, a new oral aromatase inhibitor: randomised trial comparing 2.5 mg daily, 0.5 mg daily and aminoglutethimide in postmenopausal women with advanced breast cancer. Ann Oncol 1998; 9: 639-645. (Pubitemid 28318197)
113. Geisler J, Haynes B, Anker G et al. Influence of letrozole and anastrozole on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized, cross-over study. J Clin Oncol. 2002; 20: 751-757. (Pubitemid 34111382)
114. Bonneterre J, Buzdar A, Nabholtz JM et al. Anastrozole is superior to tamoxifen as firstline therapy in hormone receptor positive advanced breast carcinoma. Cancer 2001; 92: 2247-2258. (Pubitemid 32391231)
115. Thurlimann B, Hess D, Köberle D et al. Anastrozole (« Arimidex» ) versus tamoxifen as first-line therapy in postmenopausal women with advanced breast cancer: results of the double-blind cross-over SAKK trial 21/95-a sub-study of the TARGET (Tamoxifen or « Arimidex» Randomized Group Efficacy and Tolerability) trial. Breast Cancer Res Treat 2004; 85: 247-254. (Pubitemid 38987259)
116. Smith IE. Letrozole versus tamoxifen in the treatment of advanced breast cancer and as neoadjuvant therapy. J Steroid Biochem Mol Biol. 2003; 86: 289-293. (Pubitemid 37412567)
117. Morandi P, Rouzier R, Altundag K et al. The role of aromatase inhibitors in the adjuvant treatment of breast carcinoma: the M. D. Anderson Cancer Center evidence-based approach. Cancer. 2004; 101: 1482-1489. (Pubitemid 39318892)
118. Howell A, Cuzick J, Baum M et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet 2005; 365: 60-62. (Pubitemid 40082147)
119. Coates AS, Keshaviah A, Thurlimann B et al. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol 2007; 25: 486-1192 (Pubitemid 350002953)
120. Eiermann W, Paepke S, Appfelstaedt J et al. Preoperative treatment of postmenopausal breast cancer patients with letrozole: A randomized double-blind multicenter study. Ann Oncol 2001; 12: 1527-1532. (Pubitemid 34065880)
121. Yamamoto Y, Iwase H. Safety profiles of aromatase inhibitors and selective estrogen-receptor modulators in the treatment of early breast cancer. Int J Clin Oncol 2008; 13: 384-394.
122. Safi R, Kovacic A, Gaillard S et al. Coactivation of liver receptor homologue-1 by peroxisome proliferator-activated receptor gamma coactivator-lalpha on aromatase promoter II and its inhibition by activated retinoid X receptor suggest a novel target for breast-specific antiestrogen therapy. Cancer Res 2005; 65: 11762-11770. (Pubitemid 41821738)
123. Santen RJ, Song RX, Zhang Z et al. Long-term estradiol deprivation in breast cancer cells up-regulates growth factor signaling and enhances estrogen sensitivity. EndocrRelat Cancer 2005; 12 (Suppl. 1): 561-573. (Pubitemid 41395414)
124. Sogon T, Masamura S, Hayashi S et al. Demethylation of promoter C region of estrogen receptor alpha gene is correlated with its enhanced expression in estrogen-ablation resistant MCF-7 cells. J Steroid Biochem Mol Biol 2007; 105: 106-114. (Pubitemid 47211950)
125. Eckmann KR, Kockler DR. Aromatase inhibitors in polycystic ovary syndrome. Ann Pharmacother 2009; 43: 1338-1346.
126. Requena A, Herrero J, Landeras J et al. Use of letrozole in assisted reproduction: a systematic review and meta-analysis. Hum Reprod Update 2008; 14: 571-582.
127. Attar E, Bulun SE. Aromatase inhibitors: the next generation of therapeutics for endometriosis? Fertil Steril 2006; 85: 1307-1318.
128. Dunkel L. Use of aromatase inhibitors to increase final height. Mol Cell Endocrinol 2006; 254-255: 207-216. (Pubitemid 44041744)
129. Mauras N, Bishop K, Merinbaum D et al. Pharmacokinetics and pharmacodynamics of anastrozole in pubertal boys with recent-onset gynecomastia. J Clin Endocrinol Metab 2009; 94: 2975-2978.