Understanding the pathological manifestations of aromatase excess syndrome: lessons for clinical diagnosis

References

• 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;348:1855-65
   PubMed Web of Science ®Google Scholar
• Nowakowski H, Lenz W. Genetic aspects in male hypogonadism. Recent Prog Horm Res 1961;17:53-95
   PubMedGoogle Scholar
• Wallach EE, Garcia CR. Familial gynecomastia without hypogonadism: a report of three cases in one family. J Clin Endocrinol Metab 1962;22:1201-6
   PubMedGoogle Scholar
• Hemsell DL, Edman CD, Marks JF, et al. Massive extranglandular aromatization of plasma androstenedione resulting in feminization of a prepubertal boy. J Clin Invest 1977;60:455-64
   PubMedGoogle Scholar
• Berkovitz GD, Guerami A, Brown TR, et al. Familial gynecomastia with increased extraglandular aromatization of plasma carbon19-steroids. J Clin Invest 1985;75:1763-9
   PubMedGoogle Scholar
• 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;83:1348-57
   PubMed Web of Science ®Google Scholar
• Demura M, Martin RM, Shozu M, et al. Regional rearrangements in chromosome 15q21 cause formation of cryptic promoters for the CYP19 (aromatase) gene. Hum Mol Genet 2007;16:2529-41
   PubMedGoogle Scholar
• Fukami M, Shozu M, Soneda S, et al. Aromatase excess syndrome: identification of cryptic duplications and deletions leading to gain of function of CYP19A1 and assessment of phenotypic determinants. J Clin Endocrinol Metab 2011;96:E1035-43
   Google Scholar
• Fukami M, Suzuki J, Nakabayashi K, et al. Lack of genomic rearrangements involving the aromatase gene CYP19A1 in breast cancer. Breast Cancer 2014;21(3):382-5
   PubMedGoogle Scholar
• Shihara D, Miyado M, Nakabayashi K, et al. Aromatase excess syndrome in a family with upstream deletion of CYP19A1. Clin Endocrinol 2013. [Epub ahead of print]
   PubMedGoogle Scholar
• Sebastian S, Takayama K, Shozu M, Bulun SE. 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;16:2243-54
   PubMedGoogle Scholar
• Bulun SE, Sebastian S, Takayama K, et al. The human CYP19 (aromatase P450) gene: update on physiologic roles and genomic organization of promoters. J Steroid Biochem Mol Biol 2003;86:219-24
   PubMed Web of Science ®Google Scholar
• Shozu M, Zhao Y, Bulun SE, Simpson ER. Multiple splicing events involved in regulation of human aromatase expression by a novel promoter, I.6. Endocrinology 1998;139:1610-17
   PubMed Web of Science ®Google Scholar
• Bulun SE, Takayama K, Suzuki T, et al. Organization of the human aromatase p450 (CYP19) gene. Semin Reprod Med 2004;22:5-9
   PubMed Web of Science ®Google Scholar
• Sumitani H, Shozu M, Segawa T, et al. In situ estrogen synthesized by aromatase P450 in uterine leiomyoma cells promotes cell growth probably via an autocrine/intracrine mechanism. Endocrinology 2000;141:3852-61
   PubMed Web of Science ®Google Scholar
• Shozu M, Murakami K, Inoue M. Aromatase and leiomyoma of the uterus. Semin Reprod Med 2004;22:51-60
   PubMed Web of Science ®Google Scholar
• Shozu M, Sumitani H, Segawa T, et al. Overexpression of aromatase P450 in leiomyoma tissue is driven primarily through promoter I.4 of the aromatase P450 gene (CYP19). J Clin Endocrinol Metab 2002;87:2540-8
   PubMed Web of Science ®Google Scholar
• Kasai T, Shozu M, Murakami K, et al. Increased expression of type I 17beta-hydroxysteroid dehydrogenase enhances in situ production of estradiol in uterine leiomyoma. J Clin Endocrinol Metab 2004;89:5661-8
   PubMedGoogle Scholar
• Ishikawa H, Reierstad S, Demura M, et al. High aromatase expression in uterine leiomyoma tissues of African-American women. J Clin Endocrinol Metab 2009;94:1752-6
   PubMed Web of Science ®Google Scholar
• Shozu M, Akasofu K, Harada T, Kubota Y. A new cause of female pseudohermaphroditism: placental aromatase deficiency. J Clin Endocrinol Metab 1991;72:560-6
   PubMed Web of Science ®Google Scholar
• 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;88:3027-34
   PubMed Web of Science ®Google Scholar
• Tiulpakov A, Kalintchenko N, Semitcheva T, et al. A potential rearrangement between CYP19 and TRPM7 genes on chromosome 15q21.2 as a cause of aromatase excess syndrome. J Clin Endocrinol Metab 2005;90:4184-90
   PubMedGoogle Scholar
• Sher ES, Migeon CJ, Berkovitz GD. Evaluation of boys with marked breast development at puberty. Clin Pediatr 1998;37:367-71
   PubMedGoogle Scholar
• Siiteri PK, MacDonald PC. Role of extraglandular estrogen in human endocrinology. In: Handbook of physiology: endocrinology (volume 2): female reproductive system section 7. American Physiological Society; Washington, DC: 1973. 615-29
   Google Scholar
• Schweikert HU, Milewich L, Wilson JD. Aromatization of androstenedione by isolated human hairs. J Clin Endocrinol Metab 1975;40:413-17
   PubMed Web of Science ®Google Scholar
• Schweikert HU, Milewich L, Wilson JD. Aromatization of androstenedione by cultured human fibroblasts. J Clin Endocrinol Metab 1976;43:785-95
   PubMed Web of Science ®Google Scholar
• George FW, Wilson JD. Pathogenesis of the henny feathering trait in the Sebright bantam chicken. Increased conversion of androgen to estrogen in skin. J Clin Invest 1980;66:57-65
   PubMedGoogle Scholar
• McPhaul MJ, Matsumine H, Herbst MA, Wilson JD. Aromatase expression in extragonadal tissues of the Sebright chicken is controlled by a retroviral promoter. Trans Assoc Am Physicians 1991;104:141-9
   PubMedGoogle Scholar
• Matsumine H, Herbst MA, Ou SH, et al. Aromatase mRNA in the extragonadal tissues of chickens with the henny-feathering trait is derived from a distinctive promoter structure that contains a segment of a retroviral long terminal repeat. Functional organization of the Sebright, Leghorn, and Campine aromatase genes. J Biol Chem 1991;266:19900-7
   PubMedGoogle Scholar
• 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;90:484-92
   PubMedGoogle Scholar
• Fukami M, Tsuchiya T, Vollbach H, et al. Genomic basis of aromatase excess syndrome: recombination- and replication-mediated rearrangements leading to CYP19A1 overexpression. J Clin Endocrinol Metab 2013;98:E2013-21
   Google Scholar
• Fukami M, Shozu M, Ogata T. Molecular bases and phenotypic determinants of aromatase excess syndrome. Int J Endocrinol 2012;2012:584807
   PubMedGoogle Scholar
• Fukami M, Miyado M, Nagasaki K, et al. Aromatase excess syndrome: a rare autosomal dominant disorder leading to pre- or peri-pubertal onset gynecomastia. Pediatr Endocrinol Rev 2014;11:298-305
   PubMedGoogle Scholar
• NHLW grants system database. http://mhlw-grants.niph.go.jp/niph/search/NIDD00.do?resrchNum=201231069A [Last accessed 14 February 2014]
   Google Scholar
• Lazala C, Saenger P. Pubertal gynecomastia. J Pediatr Endocrinol Metab 2002;15:553-60
   PubMed Web of Science ®Google Scholar
• Moore DC, Schlaepfer LV, Paunier L, Sizonenko PC. Hormonal changes during puberty: V. Transient pubertal gynecomastia: abnormal androgen-estrogen ratios. J Clin Endocrinol Metab 1984;58:492-9
   PubMed Web of Science ®Google Scholar
• Einav-Bachar R, Phillip M, Aurbach-Klipper Y, Lazar L. Prepubertal gynaecomastia: etiology, course and outcome. Clin Endocrinol (Oxf) 2004;61:55-60
   PubMedGoogle Scholar
• Wit JM, Hero M, Nunez SB. Aromatase inhibitors in pediatrics. Nat Rev Endocrinol 2012;8:135-47
   Google Scholar
• Henry NL, Giles JT, Stearns V. Aromatase inhibitor-associated musculoskeletal symptoms: etiology and strategies for management. Oncology (Williston Park) 2008;22:1401-8
   PubMed Web of Science ®Google Scholar
• de Ronde W. Therapeutic uses of aromatase inhibitors in men. Curr Opin Endocrinol Diabetes Obes 2007;14:235-40
   PubMedGoogle Scholar
• Bradley KL, Tyldesley S, Speers CH, et al. Contemporary systemic therapy for male breast cancer. Clin Breast Cancer 2014;14:31-9
   PubMedGoogle Scholar
• Huang ES, Miller WL. Effects of estradiol–17 beta on basal and luteinizing hormone releasing hormone-induced secretion of luteinizing hormone and follicle stimulating hormone by ovine pituitary cell culture. Biol Reprod 1980;23:124-34
   PubMedGoogle Scholar
• Alexander DC, Miller WL. Regulation of ovine follicle-stimulating hormone beta-chain mRNA by 17 beta-estradiol in vivo and in vitro. J Biol Chem 1982;257:2282-6
   PubMedGoogle Scholar
• Mercer JE, Phillips DJ, Clarke IJ. Short-term regulation of gonadotropin subunit mRNA levels by estrogen: studies in the hypothalamo-pituitary intact and hypothalamo-pituitary disconnected ewe. J Neuroendocrinol 1993;5:591-6
   PubMedGoogle Scholar
• Pitteloud N, Dwyer AA, DeCruz S, et al. Inhibition of luteinizing hormone secretion by testosterone in men requires aromatization for its pituitary but not its hypothalamic effects: evidence from the tandem study of normal and gonadotropin-releasing hormone-deficient men. J Clin Endocrinol Metab 2008;93:784-91
   PubMed Web of Science ®Google Scholar
• Zhang Y, Haraksingh R, Grubert F, et al. Child development and structural variation in the human genome. Child Dev 2013;84:34-48
   PubMed Web of Science ®Google Scholar
• Guillen Y, Ruiz A. Gene alterations at Drosophila inversion breakpoints provide prima facie evidence for natural selection as an explanation for rapid chromosomal evolution. BMC Genomics 2012;13:53
   PubMedGoogle Scholar