Significance of mutations in the androgen receptor gene in males with idiopathic infertility

被引:124
作者
Hiort, O
Holterhus, PM
Horter, T
Schulze, W
Kremke, B
Bals-Pratsch, M
Sinnecker, GHG
Kruse, K
机构
[1] Med Univ Lubeck, Dept Pediat, D-23538 Lubeck, Germany
[2] Univ Hamburg Altona, Childrens Hosp, Hamburg, Germany
[3] City Hosp Wolfsburg, Wolfsburg, Germany
[4] Univ Hosp Hamburg Eppendorf, Dept Androl, Hamburg, Germany
[5] Med Univ Lubeck, Dept Obstet & Gynecol, D-23538 Lubeck, Germany
关键词
D O I
10.1210/jc.85.8.2810
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Abnormal human spermatogenesis is caused by a variety of genetic and acquired conditions. Because spermatogenesis is dependent on androgens, some males may have a minimal form of androgen insensitivity,that does not inhibit virilization but impairs fertility. This has lead us to investigate the possibility of abnormalities in the androgen receptor (AR) gene in a large cohort of males suffering from infertility of unknown cause. We studied 180 males with variable impairment of spermatogenesis. In all patients, serum levels of testosterone and gonadotropins were analyzed to define an androgen sensitivity index (ASI). Single-strand conformation analysis and direct DNA sequencing of PCR-amplified blood leukocyte DNA were used to identify mutations within the whole coding region of the AR-gene. Endocrine and molecular investigations were compared with 53 normal males with proven fertility. In three infertile males, mutations in the AR were identified. Two unrelated males had the same variation within the first exon encoding for the transactivation domain of the receptor (Pro390Ser), whereas, in the third, a mutation in the hormone-binding region was characterized (Gln798Glu). All identified mutation carriers had a significantly elevated ASI. A proportion of males with idiopathic infertility carry relevant variations within the AR-gene. These males may be distinguished on the basis of hormone levels, calculating the ASI, although this index lacks specificity.
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收藏
页码:2810 / 2815
页数:6
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