Androgens and oestrogens, are acting through specific receptors, belonging to the nuclear receptor family and both androgen receptor (AR) and the two forms of oestrogen receptor, α (ER1) and β (ER2) are richly expressed in different parts of the male reproductive system.
There are several examples indicating that polymorphisms in these sex hormone receptors can be associated with some types of disease or milder dysfunction of the sex hormone regulated organs.
In the AR gene not only single nucleotide polymorphisms (SNPs) but also variation in the length of two repetitive sequences, CAG (glutamine encoding) and GGN (glycine encoding) repeats, can have an impact on the receptor function. Thus, extremely long (>40) CAG repeats are associated with Kennedys disease, a late onset disturbance in the neuromuscular function. Even variations in the normal range (1030) of CAG numbers have suggested as implicated in pathogenesis of conditions as male infertility, prostate cancer, testicular cancer and metabolic syndrome.
Less information is available as considers the impact of GGN repeat length variation but polymorhisms in this part of the AR gene have been linked to the risk of e.g. cryptorchidism and hypospadias.
In vitro studies have confirmed that AR activity varies with different CAG and GGN length and these variations may not only have influence on the effect of the natural ligand of the receptor but even modify the endocrine disrupting effect of environmental pollutants.
Less information is available as considers SNPs in the AR gene and risk of disease; however, we have recently identified a SNP which may be associated to the risk of testicular cancer.
SNPs in the ER1 and ER2 have also been reported as risk factors of pathological conditions in the male reproductive system, e.g. infertility and cryptorchidism. However, these findings need to be confirmed in more studies.