title: Primary amenorrhea in a young Polish woman with complete androgen insensitivity syndrome and Sertoli-Leydig cell tumor: identification of a new androgen receptor gene mutation and evidence of aromatase hyperactivity and apoptosis dysregulation within the tumor.
abstract: Primary amenorrhea in 46,XY females can be due to complete androgen insensitivity syndrome (CAIS), pure gonadal dysgenesis, 17-hydroxysteroid dehydrogenase deficiency, or mixed gonadal dysgenesis. The present paper describes a new de novo non-sense mutation in exon 1 (K141Z) of the androgen receptor gene (AR) and the expression in CAIS testis of aromatase, estrogen receptors, as well as proliferation- and apoptosis-associated proteins. CAIS is a rare disease characterized by absent virilization in 46,XY individuals and the development of a female phenotype despite normal or even elevated androgen levels. CAIS is usually caused by a mutation in AR, which leads to organ resistance to androgens. Testicular tumors such as Sertoli-Leydig cell tumor often develop in patients with CAIS. The immunohistochemical findings in the testes of our CAIS patient suggest that the high expression of aromatase and other molecular changes in the testis may be responsible for pubertal breast development and the increased risk of testicular tumor.
authors.affiliation: Department of Reproduction and Gynaecological Endocrinology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Jarzabek
authors.forename: Pascal
authors.initials: P
authors.lastname: Philibert
authors.forename: Mariusz
authors.initials: M
authors.lastname: Koda
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Sulkowski
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kotula-Balak
authors.forename: Barbara
authors.initials: B
authors.lastname: Bilinska
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Kottler
authors.forename: Slawomir
authors.initials: S
authors.lastname: Wolczynski
authors.forename: Charles
authors.initials: C
authors.lastname: Sultan
mesh_terms: D000328:Adult; D000568:Amenorrhea / Q000209:etiology* / Q000235:genetics; D013734:Androgen-Insensitivity Syndrome / Q000150:complications* / Q000201:enzymology / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics*; D001141:Aromatase / Q000378:metabolism*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D011044:Poland; D011944:Receptors, Androgen / Q000235:genetics*; D018310:Sertoli-Leydig Cell Tumor / Q000150:complications* / Q000201:enzymology / Q000235:genetics; D013736:Testicular Neoplasms / Q000150:complications* / Q000201:enzymology / Q000235:genetics / Q000473:pathology
chemical_list: D011944:Receptors, Androgen; D001141:Aromatase