The biological actions of androgens are mediated through the androgen receptor, which is a member of the nuclear receptor family and is encoded by the androgen receptor gene (AR), located on the long arm of the X chromosome. Exon1 of the AR has two polymorphic regions comprised by repetitive sequence, the CAG and the GGN repeats, encoding for (poly)glutamine and (poly)glycin, respectively. In vivo as well as in vitro studies have indicated an association between the CAG repeat number and the transactivating activity of the AR. On the other hand, little was known about the functional impact of the variation in the GGN number.

Based on in vivo and in vitro data we have provided evidence that the most common GGN alleles, GGN=23 is associated with the most optimal function of the receptor. Subjects with higher or lower GGN number are at higher risk of some of following reproductive disorders: lower ejaculate volume, infertility, cryptorchidism and/or hypospadias. CAG repeat number may not only regulate the function of the androgen receptor but also modify the effect of the persistent organohalogen pollutant on the receptor function thereby adding to the inter-individual variation in the susceptibility to such chemicals. An evidence for such effect was found on an epidemiological level and also in vitro One of the mechanisms behind this gene-environment interaction might be CAG repeat number dependent effect of co-factors on the receptor function. Although the physiological role and mechanisms behind the association between the AR polymorphisms and the receptor function is not completely understood, the available data indicate that digging into these processes may clinically and biologically important information regarding the regulation of male reproductive health.