THE ANDROGEN RECEPTOR GGN POLYMORPHISM. Genetic and functional analyses.

Male sex development and reproductive function is regulated by androgens acting via the androgen receptor (AR). The AR harbours two polymorphic repeats of CAG and GGN triplets, encoding glutamines and glycines, respectively. Both polymorphisms affect the AR transactivation ability, although the function of the GGN repeat was virtually unknown at the start of this project. Thus, the main purpose with this thesis was to study the in vivo and in vitro impact of GGN repeat variation on AR function. A reliable method for studying the segment was established, after which the GGN repeat was studied in normal men, and in men with androgen-related disorders such as prostate cancer, testicular cancer, infertility, cryptorchidism, and hypospadias. Two predominant alleles of 23 and 24 GGN repeats, respectively, were found in all subject categories studied. GGN23 was the most common allele in all men except cryptorchid men and boys with penile hypospadias, in whom GGN24 was predominant. Point mutations within the GGN repeat were present in ~1% of the Swedish population, and were not associated with severe genital malformations. In normal men, GGN