The aromatase excess syndrome is associated with feminization of both sexes and autosomal dominant transmission of aberrant p450 aromatase gene transcription

Journal of Clinical Endocrinology and Metabolism

Volumn 83, Issue 4, 1998, Pages 1348-1357

  Stratakis, Constantine A ^a,d   Vottero, Alessandra ^a   Brodie, Angela ^b   Kirschner, Lawrence S ^a   Deatkine, David ^c   Lu, Qing ^b   Yue, Wei ^b   Mitsiades, Constantine S ^a   Flor, Armando W ^d   Chrousos, George P ^a  

^a EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT   (United States)

^b UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^c St Vincent's Hospital   (United States)

^d GEORGETOWN UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROSTENEDIONE; AROMATASE; AROMATASE INHIBITOR; CHORIONIC GONADOTROPIN; COMPLEMENTARY DNA; CORTICOTROPIN; CYTOCHROME P450; ESTRONE; GONADORELIN; GONADORELIN DERIVATIVE; HISTRELIN; MESSENGER RNA; TESTOLACTONE; TRITIUM;

ARTICLE; AUTOSOMAL DOMINANT INHERITANCE; CASE REPORT; CHILD; ENZYME ACTIVITY; FEMINIZATION; GENETIC LINKAGE; GENETIC TRANSCRIPTION; GYNECOMASTIA; HUMAN; HUMAN CELL; INTRAVENOUS DRUG ADMINISTRATION; MALE; ORAL DRUG ADMINISTRATION; PRECOCIOUS PUBERTY; PRIORITY JOURNAL; SUBCUTANEOUS DRUG ADMINISTRATION;

ADULT; AROMATASE; BASE SEQUENCE; BLOTTING, WESTERN; CELL LINE; CHILD; EXONS; FEMALE; FEMINIZATION; GENES, DOMINANT; GYNECOMASTIA; HUMANS; IMMUNOHISTOCHEMISTRY; LINKAGE (GENETICS); MALE; MOLECULAR SEQUENCE DATA; PEDIGREE; SYNDROME; TRANSCRIPTION, GENETIC;

HUMAN HERPESVIRUS 4; TRITIUM;

EID: 15144341064     PISSN: 0021972X     EISSN: None     Source Type: Journal    
DOI: 10.1210/jc.83.4.1348     Document Type: Article

References (65)

1. Carlson HE. 1480 Gynecomastia. N Engl J Med. 303:795-794.
2. Braunstein GD. 1993 Gynecomastia. N Engl J Med. 328:490-495.
3. Nuttall FQ. 1974 Gynecomastia as a physical finding in normal men. J Clin Endocrinol Metab. 48:338-340.
4. August GP, Chandra R, Hung W. 1972 Prepubertal male gynecomastia. J Pediatr. 80:259-263.
5. Ljunberg T. 1960 Hereditary gynecomastia. Acta Med Scand. 168:371-379.
6. Wallach EE, Garcia C-R. 1962 Familial gynecomastia without hypogonadism: a report of three cases in one family. J Clin Endocrinol Metab. 22:1201-1206.
7. Hemsell DL, Edman CD, Marks JF, Siiteri PK, MacDonald PC. 1977 Massive extraglandular aromatization of plasma andronestedione resulting in feminization of a prepubertal boy. J Clin Invest. 60:455-464.
8. Berkovitz GD, Guerami A, Brown TR, MacDonald PC, Migeon CJ. 1985 Familial gynecomastia with increased extraglandular aromatization of plasma carbon-19 steroids. J Clin Invest. 75:1763-1769.
9. Moore DC, Schlaepfer LV, Paunier L, Sizonenko PC. 1984 Hormonal changes during puberty V. Transient pubertal gynecomastia: abnormal androgen-estrogen ratios. J Clin Endocrinol Metab. 58:492-499.
10. Bulard J, Mowszowicz I, Schaison G. 1987 Increased aromatase activity in pubic skin fibroblasts from patients with isolated gynecomastia. J Clin Endocrinol Metab. 64:618-623.
11. Simpson ER, Mahendroo MS, Means GD, et al. 1994 Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev. 15:342-355.
12. Chen S, Besman MJ, Sparkes RS, et al. 1988 Human aromatase: cDNA cloning, Southern blot analysis, and assignment of the gene to chromosome 15. DNA. 7:27-38.
13. Toda K, Terashima M, Kawamoto M, et al. 1990 Structural and functional characterization of human aromntase P450 gene. Eur J Biochem. 193:559-565.
14. Youngblood GL, Nesbitt MN, Payne AH. 1989 The structural genes encoding P450scc and P450arom are closely linked on mouse chromosome 9. Endocrinology 125:2784-2786.
15. Mahendroo MS, Mendelson CR, Simpson ER. 1993 Tissue-specific and hormonally controlled alternative promoters regulate aromatase cytochrome p450 gene expression in human adipose tissue. J Biol Chem. 268:19463-19470.
16. Harada N, Utsumi T, Takagi Y. 1993 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. 90:11312-11316.
17. Honda S, Harada N, Takagi Y. 1994 Novel exon 1 of the aromatase gene specific for aromatase transcripts in human brain. Biochem Biophys Res Commun. 198:1153-1160.
18. Toda K, Simpson ER, Mendelson CR, Shizuta Y, Kilgore MW. 1994 Expression of the gene encoding aromatase cytochrome P450 (CYP19) in fetal tissues. Mol Endocrinol. 8:210-217.
19. Wang J, Chen S. 1992 Identification of a promoter and a silencer at the 3′-end of the first intron of the human aromatase gene. Mol Endocrinol. 6:1479-1488.
20. Yamada K, Harada N, Honda S, Takagi Y. 1995 Regulation of placenta-specific expression of the aromatase cytochrome P-450 gene. J Biol Chem. 270:25064-25069.
21. Zhao Y, Mendelson CR, Simpson ER. 1995 Characterization of the sequences of the human CYP19 (aromatase) gene that mediate regulation by glucocorticoids in adipose stromal cells and fetal hepatocytes. Mol Endocrinol. 9:340-349.
22. Michael DM, Kilgore MW, Morohashi K, Simpson ER. 1995 Ad4BP/SF1 regulates cyclicAMP-induced transcription from the proximal promoter (PII) of the human aromatase P450 (CYP19) gene in the ovary. J Biol Chem. 270:13561-13566.
23. Jacob F, Homann D, Seuferf J, Schneider D, Kohrle J. 1995 Expression and regulation of aromatase cytochrome P450 in THP I human myeloid leukaemia cells. Mol Cell Endocrinol. 110:27-33.
24. Harada N, Utsumi T, Takagi Y. 1995 Molecular and epidemiological analyses of abnormal expression of aromatase in breast cancer. Pharmacogenetics 5: S59-S64.
25. Bulun SE, Rosenthal IM, Brodie AMH et al. 1993 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. 77:1616-1621.
26. Bulun SE, Economos K, Miller D, Simpson ER. 1994 CYP19 (aromatase cytochrome P450) gene expression in human malignant endometrial tumors. J Clin Endocrinol Metab. 79:1831-1834.
27. George FW, Wilson JD. 1980 Pathogenesis of the henny feathering trait in the Sebright bantam chicken. J Clin Invest. 66:57-65.
28. Leshin M, Baron J, George FW, Wilson JD. 1981 Increased estrogen formation and aromatase activity in fibroblasts cultured from the skin of chickens with the henny feathering trait. J Biol Chem. 256:4341-4344.
29. Saez JM, Forest MG. 1979 Kinetics of human chorionic gonadotropin-induced steroidogenic response of the human testis. I. Plasma testosterone:implications for human chorionic gonadotropin stimulation test. J Clin Endocrinol Metab 49:278-283.
30. 4-andonestedione, estrone, and 17β-estradiol: evidence for the action of human chorionic gonadotropin on intermediate enzymes implicated in steroid biosynthesis. J Clin Endocrinol Metab. 49:284-291.
31. Forest MG. 1984 Maturation of human testicular response to hCG. Ann NY Acad Sci. 438:304-328.
32. Greulich WW, Pyle SI. 1959 Radiographic atlas of skeletal development of the hand and wrist. Stanford: Stanford University Press.
33. Zachman M, Sobradillo B, Frank M, et al. 1978 Height predictions in normal children and in patients with various pathologic conditions. J Pediatr. 93:749-755.
34. Oerter KE, Manasco P, Barnes KM, Jones J, Hill S, Cutler GB. 1991 Adult height in precocious puberty after long-term treatment with deslorelin. J Clin Endocrinol Metab. 73:1235-1240.
35. Feuillan-Philbrick P, Jones J, Cutler GB. 1993 Long-term testolactone therapy for precocious puberty in girls with the McCune-Albright syndrome. J Clin Endocrinol Metab. 77:647-651.
36. Stratakis CA, Carney JA, Lin JP, et al. 1996 Carney complex, a multiple endocrine neoplasia and familial lentiginosis syndrome: analysis of 11 kindreds and linkage to the short arm of chromosome 2 (2p16). J Clin Invest. 97:599-607.
37. Brodie AMH, Inkster SE. 1993 Aromatase in the human testis. J Steroid Biochem Mol Biol. 44:549-555.
38. Inkster S, Yue W, Brodie A. 1995 Human testicular aromatase: immunocytochemical and biochemical studies. J Clin Endcorinol Metab. 80:1941-1947.
39. Lu Q, Nakmura J, Savinov A, et al. 1996 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 137:3061-3068.
40. Hurley DM, Accili D, Stratakis CA, et al. 1991 Point mutation causing a single amino acid substitution in the hormone binding domain of the glucocorticoid receptor in familial glucocosticoid resistance. J Clin Invest. 87:680-686.
41. Stratakis CA, Orban Z, Burns AL, et al. 1996 Dideoxyfingerprinting (ddF) analysis of the type × collagen gene (COL10A1) and identification of a novel mutation (S671P) in a kindred with Schmid metaphyseal chondrodysplasia. Biochem Mol Med. 59:112-117.
42. Sourdaine P, Parker MG, Telford J, Miller WR. 1994 Analysis of the aromatase cytochrome P450 gene in human breast cancers. J Mol Endocrinol. 133:331-337.
43. Jenkins C, Michael D, Mahendroo M, Simpson E. 1993 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. 97:R1-R6.
44. Bellino FL, Tseng L, Lobo JO. 1987 Antisera against estrogen synthetase from human placental microsomes. Antibody characterization and cross-reactivity studies in other organs. Mol Cell Endocrinol. 52:143-150.
45. Polymeropoulos MH, Xiao H, Rath DS, Merril CR. 1991 Tetranucleotide repeat polymorphism at the human aromatase cytochrome P-450 gene (CYP19). Nucleic Acids Res. 19:195.
46. Lathrop GM, Lalouel JM, Julier C, Ott J. 1984 Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci USA. 81:3443-3446.
47. Magiakou MA, Mastorakos G, Oldfield EH, et al. 1994 Cushing syndrome in children and adolescents: presentation, diagnosis and therapy. N Engl J Med. 331:629-635.
48. Forest MG. 1979 Pattern of the response to testosterone and of its precursors to hCG stimulation in relation to age in infants and children. J Clin Endocrinol Metab. 49:132-137.
49. Oerter KE, Uriarte M, Rose SR, Barnes KM, Cutler GB. 1990 Gonadotropin secretory dynamics during puberty in normal girls and boys. J Clin Endocrinol Metab. 71:1251-1258.
50. Lashansky G, Saenger P, Fishman K, et al. 1991 Normative data for adrenal steroidogenesis in a healthy pediatric population: age and sex-related changes after adrenocorticotropin stimulation. J Clin Endocrinol Metab. 73:674-686.
51. 50a. Vottero A, Kirschner LS, Vue W, Brodie A, Stratakis CA. 1998 Aromatase expression in peripheral blood lymphocytes before and after Epstein-Barr virus (EBV) transformation. J Ster Biochem Mol Biol. In press.
52. Berstein LM, Santner SJ, Brodie AM, Koos RD, Naftolin F, Santen RJ. Pseudoaromatase in circulating lymphocytes. J Steroid Biochem Mol Biol. 44:647-649.
53. Leiberman E, Zachmann M. 1992 Familial adrenal feminization probably due to increased steroid aromatization. Horm Res. 37:96-102.
54. Morishima A, Grumbach MM, Smpson ER, Fisher C, Qin K. 1995 Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metab. 80:3689-3698.
55. Finkelstein JS, O'Dea LS, Whitcomb RW, Crowley WF. 1991 Sex steroid control of gonadotropin secretion in the human male. II. Effects of estradiol administration in normal and GnRH-deficient men. J Clin Endocrinol Metab. 74:621-628.
56. Bagatell CJ, Dahl KD, Bremmer WJ. 1994 The direct pituitary effect of testosterone to inhibit gonadotropin secretion in men is partially mediated by aromatization to estradiol. J Androl. 15:15-21.
57. Grumbach MM, Styne D. 1992 Puberty: ontogeny, neuroendocrinology, physiology, and disorders. In: Wilson JD, Foster DW, eds. Williams' textbook of endocrinology, 8th ed. Philadeplhia: Saunders; 1139-1221.
58. Conte FA, Grumbach MM, Ito Y, Fisher CR, Simpson ER. 1994 A syndrome of female pseudohermaphroditism, hypergonadotropic hypogonadism, and multicystic ovaries associated with missense mutations in the gene encoding aromatase (P450arom). J Clin Endocrinol Metab. 78:1287-1292.
59. Ito Y, Fisher CR, Conte FA, Grumbach MM, Simpson ER. 1993 Molecular basis of aromatase deficiency in an adult female with sexual infantilism and polycystic ovaries. Proc Natl Acad Sci USA 90:11673-11677.
60. Harada N. 1993 Genetic analysis of human placental aromatase deficiency. J Steroid Biochem Mol Biol. 44:331-340.
61. Smith EP, Boyd J, Frank GR, et al. 1994 Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med. 331:1056-1061.
62. Carani C, Qin K, Simoni M, et al. 1997 Effect of testosterone and estradiol in a man with aromatase deficiency. N Engl J Med. 337:91-95.
63. Agarwal VR, Sasano H, Takayama K, et al. Excessive levels of aromatase P450arom and its transcripts in breast adipose tissue of a girl with pubertal macromasria [Abstract P1-393]. Proc of the 79th Annual Meet of The Endocrine Soc. 1997.
64. Sasano H, Kimura M, Shizawa S, Kimura N, Nagura H. 1997 Aromatase and steroid receptors in gynecomastia and male breast carcinoma: an immunohistochemical study. J Clin Endocrinol Metab. 81:3063-3067.
65. Gelinas R, Endlich B, Pfeiffer C, Yagi M, Stamatoyannopoulos G. 1985 G to A substitution in the distal CCAAT box of the γ-globin gene in Greek hereditary persistence of fetal hemoglobin. Nature 313:323-325.