Functional in vitro characterisation of the androgen receptor GGN polymorphism

Abstract

Superior androgen receptor (AR) function in subjects carrying a GGN repeat length of 23 (GGN23) has been indicated in vivo. Therefore, the activity of the AR carrying GGN23 combined with CAG22 was compared to the AR with GGN10, 24 and 27, respectively, in the presence of 0.1-100 nM testosterone or DHT. At 100 nM DHT, GGN24 showed 35% lower transactivating activity (95% [CI]: 20-50%) than GGN23. GGN10 and GGN27 also showed significantly less AR activity than GGN23 (mean differences [95% CI]: 54% [40-68%] and 58% [39-78%], respectively). The same trend was also observed at lower DHT concentrations. In response to R1881, GGN23 activity was significantly higher than for other lengths. ARs with other glutamine numbers than 23 have lower transactivating capacity in response to both testosterone and DHT. Congenital malformations and other signs of hypoandrogenism in subjects with AR gene GGN lengths other than 23 could, hence, be related to a lower AR activity. © 2006 Elsevier Ireland Ltd. All rights reserved.