Aromatase: Biologic Relevance of Tissue-Specific Expression

Seminars in Reproductive Medicine

Volumn 22, Issue 1, 2004, Pages 11-23

  Simpson, Evan R ^a,b  

^a MONASH MEDICAL CENTRE   (Australia)

^b MONASH UNIVERSITY   (Australia)

Author keywords

Adipose tissue; Aromatase P450; Bone; Local estrogen biosynthesis; Ovary; P450arom; Placenta

Indexed keywords

AROMATASE; CYTOCHROME P450; ESTROGEN;

ADIPOSE TISSUE; BONE; BRAIN; CANCER CELL; ENZYME MECHANISM; ESTROGEN SYNTHESIS; GENE EXPRESSION; HUMAN; HUMAN TISSUE; OVARY; PLACENTA; PROMOTER REGION; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; TISSUE SPECIFICITY;

AROMATASE; ESTROGENS; GENE EXPRESSION; HUMANS; NEOPLASMS; TISSUE DISTRIBUTION;

EID: 1942422264     PISSN: 15268004     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2004-823023     Document Type: Review

References (89)

1. Nelson DR, Koymans L, Kamataki T, et al. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 1996;6:1-42
2. Means GD, Mahendroo M, 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
3. Harada N, Yamada K, Saito K, Kibe N, Dohmae S, Takagi Y. Structural characterization of the human estrogen synthetase (aromatase) gene. Biochem Biophys Res Commun 1990;166: 365-372
4. Toda K, Terashima M, Kamamoto T, et al. Structural and functional characterization of human aromatase P450 gene. Eur J Biochem 1990;193:559-565
5. Means GD, Kilgore MW, Mahendroo MS, Mendelson CR, Simpson ER. Tissue-specific promoters regulate aromatase cytochrome P450 gene expression in human ovary and fetal tissues. Mol Endocrinol 1991;5:2005-2013
6. arom: the promoter responsible for expression in adipose is different from that utilized in placenta. J Biol Chem 1991;266:11276-11281
7. a. Sebastian 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
8. Jenkins C, Michael D, Mahendroo M, Simpson E. Exon-specific northern analysis and rapid amplification of cDNA ends (RACE) reveal that the proximal promoter II (PII) is responsible for aromatase cytochrome P450 (CYP19) expression in human ovary. Mol Cell Endocrinol 1993;97:R1-R6
9. Mahendroo MS, Mendelson CR, Simpson ER. Tissue-specific and hormonally-controlled alternative promoters regulate aromatase cytochrome P450 gene expression in human adipose tissue. J Biol Chem 1993;268:19463-19470
10. Honda S, Harada N, Takagi N. Novel exon I of the aromatase gene specific for aromatase transcripts in human brain. Biochem Biophys Res Commun 1994;198:1153-1160
11. Shozu M, Zhao Y, Bulun SE, Simpson ER. Multiple splicing events involved in regulation of human aromatase expression by a novel promoter, 1.6. Endocrinology 1998;139:1610-1617
12. Simpson ER, Zhao Y, Agarwal VR, et al. Aromatase expression in health and disease. Recent Prog Horm Res 1997;52:185-214
13. Callard GV, Petro Z, Ryan KJ. Phylogenetic distribution of aromatase and other androgen-converting enzymes in the central nervous system. Endocrinology 1978;103:2283-2290
14. Callard GV, Petro Z, Ryan KJ. Aromatization and 5α-reduction in brain and non-neural tissues of a cyclostome (Petromyzan marinua). Gen Comp Endocrinol 1980;42:155-159
15. Callard GV. Aromatization is cyclic AMP-dependent in cultured reptilian brain cells. Brain Res 1981;204:451-454
16. Hutchinson JB. Hormonal control of behaviour: steroid action in the brain. Curr Opin Neurobiol 1991;1:562-570
17. Michael MD, Kilgore MW, Morohashi K, Simpson ER. Ad4BP/SF-1 regulates cyclic AMP-induced transcription from the proximal promoter (PII) of the human aromatase P450 (CYP19) gene in the ovary. J Biol Chem 1995;270: 13561-13566
18. Fitzpatrick SL, Richards JS. Identification of a cyclic adenosine 3′,5′-monophosphate-response element in the rat aromatase promoter that is required for transcriptional activation in rat granulose cells and R2C leydig cells. Mol Endocrinol 1994;8:1309-1319
19. Luo X, Ikeda Y, Parker KL. A cell-specific nuclear receptor is essential for adrenal and gonadal development. Cell 1994;77: 481-490
20. Lala DS, Rice DA, Parker KL. Steroidogenic factor 1, a key regulation of steroidogenic gene expression, is the mouse homolog of fushi tarazu-factor 1. Mol Endocrinol 1992;6: 1249-1258
21. Michael MD, Michael LF, Simpson ER. A CRE-like sequence that binds CREB and contributes to cAMP-dependent regulation of the proximal promoter of the human aromatase P450 (CYP19) gene. Mol Cell Endocrinol 1997;134:147-156
22. Hinshelwood MM, Michael MD, Simpson ER. The 5′-flanking region of the ovarian promoter of the bovine CYP19 gene contains a deletion in a cyclicadenosine 3′,5′-monophosphate-like responsive sequence. Endocrinology 1997;138: 3704-3710
23. Zhao Y, Mendelson CR, Simpson ER. Characterization of the sequences of the human CYP19 (aromatase) gene that mediate regulation by glucocorticoids in adipose stromal cells and fetal hepatocytes. Mol Endocrinol 1995;9:340-349
24. Zhao Y, Nichols JE, Bulun SE, Mendelson CR, Simpson ER. Aromatase P450 gene expression in human adipose tissue: role of a Jak/STAT pathway in regulation of the adipose-specific promoter. J Biol Chem 1995;270:16449-16457
25. Reichardt HM, Schutz G. Glucocorticoid signalling: multiple variations of a common theme. Mol Cell Endocrinol 1998; 146:1-6
26. Price T, O'Brien S, Dunaif A, Simpson ER. Comparison of aromatase cytochrome P450 mRNA levels in adipose tissue from the abdomen and buttock using competitive polymerase chain reaction amplification. Proc Soc Gynecol Invest 1992; 1:179
27. Berkovitz GD, Bisat T, Carter KM. Aromatase activity in microsomal preparations of human genital skin fibroblasts: influence of glucocorticoids. J Steroid Biochem 1989;33:341-347
28. Bruch HR, Wolf L, Budde R, Romalo G, Schweikert HU. Androstenedione metabolism in cultured human osteoblast-like cells. J Clin Endocrinol Metab 1992;75:101-105
29. Nawata H, Tanaka S, Tanaka S, et al. Aromatase in bone cell: association with osteoporosis in postmenopausal women. J Steroid Biochem Mol Biol 1995;53:165-174
30. Harada N, Utsume T, Takagi Y. Tissue-specific expression of the human aromatase cytochrome P-450 gene by alternative use of multiple exons 1 and promoters, and switching of tissue-specific exons 1 in carcinogenesis. Proc Natl Acad Sci USA 1993;90:11312-11316
31. Agarwal VR, Bulun SE, Leitch M, Rohrich R, Simpson ER. Use of alternative promoters to express the aromatase cytochrome P450 (CYP19) gene in breast adipose tissues of cancer-free and breast cancer patients. J Clin Endocrinol Metab 1996;81:3843-3849
32. 2 via cyclic AMP, leading to activation of promoter II of the CYP19 (aromatase) gene. Endocrinology 1996;137: 5739-5742
33. Agarwal VR, Ashanullah CI, Simpson ER, Bulun SE. Alternatively spliced transcripts of the aromatase cytochrome P450 (CYP19) gene in adipose tissue of women. J Clin Endocrinol Metab 1997;82:70-74
34. 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
35. Wei J, Xu H, Davies JL, Hemmings JP. Increase of plasma IL-6 concentration with age in healthy subjects. Life Sci 1992;51:1953-1956
36. Daynes RA, Araneo BA, Ershler WB, Maloney C, Li GZ, Ryu SY. Altered regulation of IL-6 production with normal aging. J Immunol 1993;150:5219-5230
37. Petruschke T, Hauner H. Tumor necrosis factor-alpha prevents the differentiation of human adipocyte precursor cells and caused delipidation of developed fat cells. J Clin Endocrinol Metab 1993;76:742-747
38. Kawashima I, Ohsumi J, Mita-Honjo K, et al. Molecular cloning of cDNA encoding adipogenesis inhibitory factor and identity with interleukin-11. FEBS Lett 1991;283:199-202
39. Kliewer SA, Lenhard JM, Willson TM, Patel I, Morris DC, Lehmann JM. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation. Cell 1995;83:813-819
40. Rubin GL, Zhao Y, Kalus AM, Simpson ER. Peroxisome proliferator-activated receptor gamma ligands inhibit estrogen biosynthesis in human breast adipose tissue: possible implications for breast cancer therapy. Cancer Res 2000;60: 1604-1608
41. Rink JD, Simpson ER, Barnard JJ, Bulun SE. Cellular chacterization of adipose tissue from various body sites of women. J Clin Endocrinol Metab 1996;81:2443-2447
42. Bulun SE, Sharda G, Rink J, Sharma S, Simpson ER. Distribution of aromatase P450 transcripts and adipose fibroblasts in the human breast. J Clin Endocrinol Metab 1996;81:1273-1277
43. Harada N. Aberrant expression of aromatase in breast cancer tissues. J Steroid Biochem Mol Biol 1997;61:175-184
44. Zhou D, Zhou C, Chen S. Gene regulation studies of aromatase expression in breast cancer and adipose stromal cells. J Steroid Biochem Mol Biol 1997;61:273-280
45. Zhou J, Gurates B, Yang S, Sebastian S, Bulun SE. Malignant breast epithelial cells stimulate aromatase expression via promoter II in human adipose fibroblasts: an epithelial-stromal interaction in breast tumors mediated by CCAAT/enhancer binding protein beta. Cancer Res 2001;61:2328-2334
46. Meng L, Zhou J, Sasano H, Suzuki T, Zeitoun KM, Bulun SE. Tumor necrosis factor alpha and interleukin 11 secreted by malignant breast epithelial cells inhibit adipocyte differentiation by selectively down-regulating CCAAT/enhancer binding protein alpha and peroxisome proliferator-activated receptor gamma: mechanism of desmoplastic reaction. Cancer Res 2001;61:2250-2255
47. Toda K, Miyahara K, Kawamoto T, Ikeda H, Sagara Y, Shizuta Y. Characterization of a cis-acting regulatory element involved in human aromatase P450 gene expression. Eur J Biochem 1992;205:303-309
48. Yamada K, Harada N, Honda S, Takagi Y. Regulation of placenta-specific expression of the aromatase cytochrome P450 gene: involvement of the trophoblast-specific element binding protein. J Biol Chem 1995;270:25064-25069
49. Sun T, Zhao Y, Fisher CR, Kilgore M, Mendelson CR, Simpson ER. Characterization of cis-acting elements of the human aromatase P450 (CYP19) gene that mediate regulation by retinoids in human choriocarcinoma cells (abstract OR38-8). In: Program & Abstracts of the 10th International Congress of Endocrinology, Vol. 1, June 11-14, 1996, San Francisco, CA. Washington, DC: Endocrine Society
50. Stephanon A, Sarlis NJ, Richards R, Handwerger S. Expression of retinoic acid receptor subtypes and cellualr retinoic acid binding protein II in MRNAs during differentiation of human trophoblast cells. Biochem Biophys Res Commun 1994;202:772-780
51. Barak Y, Nelson MC, Ong ES, et al. PPAR gamma is required for placental, cardiac, and adipose tissue development. Mol Cell 1999;4:585-595
52. Jiang B, Kamat A, Mendelson CR. Hypoxia prevents induction of aromatase expression in human trophoblasts: potential inhibitory role of the hypoxia-inducible transcription factor Mash-2 (mammalian achaete-scute homologous protein-2). Mol Endocrinol 2000;14:1661-1673
53. Kamat A, Graves KH, Smith ME, Richardson JA, Mendelson CR. A 500-bp region, approximately 40 kb upstream of the human CYP19 (aromatase) gene, mediates placenta-specific expression in transgenic mice. Proc Natl Acad Sci USA 1999;96:4575-4580
54. 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
55. Carani C, Qin K, Simoni M, et al. Aromatase deficiency in the male: effect of testosterone and estradiol treatment. N Engl J Med 1997;337:91-95
56. arom gene: impact of estrogens on hypergonadotropic hypogonadism, multicystic ovaries, and bone densitometry in childhood. J Clin Endocrinol Metab 1997;82:1739-1745
57. Sasano H, Uzuki M, Sawai T, et al. Aromatase in bone tissue. J Bone Miner Res 1997;12:1416-1423
58. Shozu M, Simpson ER. Aromatase expression of human osteoblast-like cells. Mol Cell Endocrinol 1998;139:117-129
59. Sasano H, Frost AR, Saitoh R, et al. Aromatase and 17β -hydroxysteroid dehydrogenase type 1 in human breast carcinoma. J Clin Endocrinol Metab 1996;81:4042-4046
60. Lea CK, Ebrahim H, Tennant S, Flanagan AM. Aromatase cytochrome P450 transcripts are detected in fractured human bone but not in normal skeletal tissue. Bone 1997;21:433-440
61. Lauber ME, Lichtensteiger W. Pre- and postnatal ontogeny of aromatase cytochrome P450 messenger RNA expression in the male rat brain studied by in situ hybridization. Endocrinology 1994;135:1661-1668
62. Wagner CK, Morrell JI. Neuroanatomical distribution of aromatase in RNA in the rat brain: indications of regional regulation. J Steroid Biochem Mol Biol 1997;61:307-314
63. Sasano H, Takashashi K, Satoh F, Nagura H, Harada N. Aromatase in the central nervous system. Clin Endocrinol (Oxf) 1998;48:325-329
64. Abdelgadir SE, Resko JA, Ojeda SR, Lephart ED, McPhaul MJ, Roselli CE. Androgens regulate aromatase cytochrome P450 messenger ribonucleic acid in the rat brain. Endocrinology 1994;135:395-401
65. Abe-Dohmae S, Takagi Y, Harada N. Autonomous expression of aromatase during development of mouse brain is modulated by neurotransmitters. J Steroid Biochem Mol Biol 1997;61:299-306
66. Lanoux MJ, Cleland WH, Mendelson CR, Carr BR, Simpson ER. Factors affecting the conversion of androstenedione to estrogens by human fetal hepatocytes in monolayer culture. Endocrinology 1985;117:361-367
67. Harada N. A unique aromatase (P450arom) mRNA formed by alternative use of tissue specific exons I in human skin fibroblasts. Biochem Biophys Res Commun 1992;189:1001-1007
68. Toda K, Simpson ER, Mendelson CR, Shizuta Y, Kilgore MW. Expression of the gene encoding aromatase cytochrome P450 (CYP19) in fetal tissues. Mol Endocrinol 1994;8:210-217
69. Zeitoun K, Takayama K, Michael MD, Bulun SE. Stimulation of aromatase 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. Mol Endocrinol 1999;13:239-253
70. Harada N, Sasano H, Murakami H, Ohkuma T, Nagura H, Takagi Y. Localized expression of aromatase in human vascular tissues. Circ Res 1999;84:1285-1291
71. Sasano H, MuraKami H, Shizawa S, Satomi S, Nagura H, Harada N. Aromatase and sex steroid receptors in human vena cava. Endocr J 1999;46:233-242
72. Agarwal VR, Takayama K, Van Wyk JJ, Sasano H, Simpson ER, Bulun SE. Molecular basis of severe gynecomatsia associated with aromatase expression in a fibrolamellar hepatocellular carcinoma. J Clin Endocrinol Metab 1998;83: 1797-1800
73. Bulun SE, Rosenthal IM, Brodie AM, et al. Use of tissue-specific promoters in the regulation of aromatase cytochrome P450 gene expression in human testicular and ovarian sex cord tumors as well as in normal fetal and adult gonads. J Clin Endocrinol Metab 1994;78:1616-1621
74. Young J, Bulun SE, Agarwal V, Couzinet B, Mendelson CR. Aromatase expression in a feminizing adrenocortical tumor. J Clin Endocrinol Metab 1996;81:3173-3176
75. Bulun SE, Economos K, Miller D, Simpson ER. CYP19 (aromatase) gene expression in human malignant endometrial tumors. J Clin Endocrinol Metab 1994;79:1831-1834
76. Noble LS, Simpson ER, Johns A, Bulun SE. Aromatase expression in endometriosis. J Clin Endocrinol Metab 1996;81:174-179
77. Naftolin F, Ryan KJ, Davies IJ, et al. The formation of estrogens by central neuroendocrine tissues. Recent Prog Horm Res 1975;31:295-319
78. Siiteri PK, MacDonald PC. Role of extraglandular estrogen in human endocrinology. In: Green RO, Astwood EB, eds. Handbook of Physiology. Vol. 2. American Physiological Society; 1973:619-629
79. Melton LJ. Epidemiology of spinal osteoporosis. Spine 1997;22:2S-11S
80. Huang Z, Hankinson SE, Colditz GA, et al. Dual effects of weight and weight gain on breast cancer risk. JAMA 1997;278:1407-1411
81. Hemsell DL, Edman CD, Marks JF, Siiteri PK, MacDonald PC. Plasma precursors of estrogen, II: Correlation of the extent of conversion of plasma androstenedione to estrone with age. J Clin Endocrinol Metab 1974;38:476-479
82. Tsai-Morris CH, Aquilana DR, Dufau ML. Cellular localisation of rat testicular aromatase activity during development. Endocrinology 1985;116:38-46
83. Nitta H, Bunick D, Hess RA, et al. Germ cells of the mouse testis express P450 aromatase. Endocrinology 1993;132: 1396-1401
84. Morishima A, Grumbach MM, Simpson ER, Fisher C, Qin M. Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of oestrogens. J Clin Endocrinol Metab 1995;80:3689-3698
85. Toda K, Okada T, Akira S, et al. Oestrogen at the neonatal stage is critical for reproductive ability of male mice as revealed by supplementation with 17β-oestradiol to aromatase gene (Cyp19) knockout mice. J Endocrinol 2001;168:455-463
86. Robertson KM, Simpson ER, Lacham-Kaplan O, Jones MEE. Characterization of the fertility of the male aromatase knockout (ArKO) mouse. J Androl 2001;22:825-830
87. Labrie F, Belanger A, Luu-The V, et al. DHEA and the intracrine formation of androgens and estrogens in peripheral target tissues: its role during aging. Steroids 1998;63:322-328
88. Corbould AM, Judd SJ, Rodgers RJ. Expression of types 1,2 and 3 β-hydroxysteroid dehydrogenase in subcutaneous abdominal and intra-abdominal adipose tissue of women. J Clin Endocrinol Metab 1998;83:187-194
89. Pasqualini JR, Chetrite G, Blacker C, et al. Concentrations of estrone, estradiol and estrone sulfate and evaluation of sulfatase and aromatase activities in pre- and postmenopausal breast cancer patients. J Clin Endocrinol Metab 1996;81: 1460-1464