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.
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.
Jarzabek
Katarzyna
K
Department of Reproduction and Gynaecological Endocrinology, Medical University of Bialystok, Bialystok, Poland.
Philibert
Pascal
P
Koda
Mariusz
M
Sulkowski
Stanislaw
S
Kotula-Balak
Malgorzata
M
Bilinska
Barbara
B
Kottler
Marie-Laure
ML
Wolczynski
Slawomir
S
Sultan
Charles
C
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
D011944:Receptors, Androgen; D001141:Aromatase