{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:27:41Z","timestamp":1792168061396,"version":"4.4.0"},"reference-count":65,"publisher":"The Endocrine Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1998,4,1]]},"abstract":"<jats:p>Increased extraglandular aromatization has been reported as the cause of familial gynecomastia. We studied a kindred with aromatase excess inherited in an autosomal dominant manner, in which affected males had heterosexual precocity and\/or gynecomastia, and affected females had isosexual precocity and\/or macromastia.<\/jats:p><jats:p>The propositus was a 9-yr-old boy with gynecomastia. His 7.5-yr-old sister had precocious puberty, and their father and paternal grandmother had peripubertal gynecomastia and macromastia, respectively. Serum concentrations of gonadal and adrenal steroid hormones were determined before and after the administration of corticotropin and\/or hCG. Aromatase activity was determined by[ 3H]\u03944-androstenedione to[ 3H]estrone conversion by cultured skin fibroblasts and\/or Epstein-Barr virus-transformed lymphocytes and was detected by immunohistochemistry and\/or Western analysis. Linkage was examined with a polymorphism of the aromatase (P450arom) gene. The P450arom messenger ribonucleic acid was analyzed by rapid amplification of complementary DNA (cDNA) ends, ribonuclease protection assay, and RT-PCR.<\/jats:p><jats:p>hCG testing demonstrated a high rate of conversion of\u0394 4-androstenedione to estrone and of testosterone to estradiol in the propositus and his father. Treatment of the propositus and his sister was initiated with an aromatase inhibitor (testolactone) and a GnRH analog, which successfully delayed skeletal and pubertal development in both children. Markedly increased aromatase activity was found in the patients\u2019 fibroblasts and Epstein-Barr virus-transformed lymphocytes. The P450arom polymorphism segregated with the disease in the family. A new 5\u2032-splice variant was present in the patients\u2019 P450arom messenger ribonucleic acid, thus identifying yet another first exon of this gene, which appears to be aberrantly expressed in this family.<\/jats:p><jats:p>In conclusion, a family with the aromatase excess syndrome is described, in which the condition was inherited in an autosomal dominant manner, led to feminizing manifestations in both sexes, and was associated with the aberrant utilization of a novel transcript of the P450arom gene.<\/jats:p>","DOI":"10.1210\/jcem.83.4.4697","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T17:03:03Z","timestamp":1389200583000},"page":"1348-1357","source":"Crossref","is-referenced-by-count":12,"title":["The Aromatase Excess Syndrome Is Associated with Feminization of Both Sexes and Autosomal Dominant Transmission of Aberrant P450 Aromatase Gene Transcription1"],"prefix":"10.1210","volume":"83","author":[{"given":"Constantine 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Maryland 21201;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence S.","family":"Kirschner","sequence":"additional","affiliation":[{"name":"Section on Pediatric Endocrinology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health (C.A.S., A.V., L.S.K., C.S.M., G.P.C.), Bethesda, Maryland 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"DeAtkine","sequence":"additional","affiliation":[{"name":"Southview Medical Group\/St. Vincent\u2019s Hospital (D.D.), Birmingham, Alabama 35205;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Lu","sequence":"additional","affiliation":[{"name":"the Department of Pharmacology, University of Maryland (A.B., Q.L., W.Y.), Baltimore, Maryland 21201;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yue","sequence":"additional","affiliation":[{"name":"the Department 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