Association of polymorphisms in genes encoding hormone receptors ESR1, ESR2 and LHCGR with the risk and clinical features of testicular germ cell cancer.

Testicular germ cell cancer (TGCC) is the most common malignancy in young men. Genetic variants known to be associated with risk of TGCC only partially account for the observed familial risks. We aimed to identify additional polymorphisms associated with risk as well as histological and clinical features of TGCC in 367 patients and 214 controls. Polymorphisms in ESR2 (rs1256063; OR=0.53, 95% CI: 0.35-0.79) and LHCGR (rs4597581; OR=0.68, 95% CI: 0.51-0.89, and rs4953617; OR=1.88, 95% CI: 1.21-2.94) associated with risk of TGCC. Polymorphisms in ESR1 (rs9397080; OR=1.85, 95% CI: 1.18-2.91) and LHCGR (rs7371084; OR=2.37, 95% CI: 1.26-4.49) associated with risk of seminoma and metastasis, respectively. SNPs in ESR1 (rs9397080) and LHCGR (rs7371084) were predictors of higher LH levels and higher androgen sensitivity index in healthy subjects. The results suggest that polymorphisms in ESR1, ESR2 and LHCGR contribute to the risk of developing TGCC, histological subtype, and risk to metastasis

Identification and Structural Analysis of the Androgen Receptor From Normal and Androgen Insensitive Human Fibroblasts

Resistance to androgens in utero and at puberty causes a dysfunction of male sexual differentiation, and results in a form of male pseudohermaphroditism. From whole cell binding studies, using cultured human genital skin fibroblasts (GSF) a number of defects in the androgen receptor have been discovered, these have been classified as: absent, deficient, thermolabile, defective activation to the DNA/nuclear binding form, and finally, failure to "up-regulate" the basal binding level in response to prolonged (i.e. 24h) incubation of cells with hormone. There is, however, a need to study the receptor protein directly, without relying on the reversible binding of 3H ligand. Therefore, in the present study the androgen receptor from human GSF was extracted using 0.5M-KCl, and partially purified by 35% ammonium sulphate preciptitation prior to further studies