Current Evidence for the Involvement of Hypogonadism and Modulation of Steroid Receptors in Prostate Carcinoma

Abstract

Prostate cancer (PCa) is the most prevalent cancer in the Nigerian male population, similar to other black populations. It is postulated that exposure to endogenous or environmental steroids prompts prostatic mediated changes via steroid receptors as well as a decrease in the androgen/estrogen ratio and aging. Thereby contributing to prostatic carcinogenesis and disease progression. This study is aimed to determine the plasma levels of testosterone, 17β-estradiol as well as the pattern of expression of steroid receptors in subjects with prostate cancer, benign prostatic hyperplasia, and controls. Study participants are made up of a total of 195 consented volunteers consisting of 65 Prostate cancer (PCa) and 65 benign prostatic hyperplasia (BPH) treatment naïve participants and 65 apparently healthy subjects as controls. Anthropometric data were measured using standard methods and biochemical parameters determined by enzyme-linked immunosorbent assay (ELISA). The gene expression is quantified by Real-Time PCR with PerfeCTa SYBR Green SuperMix on CFX96 Bio-Rad, USA. The results of this study showed increased levels of 17β-estradiol, total androgen receptor (AR) and estrogen receptor-beta (Erβ) in prostate cancer participants compared with controls (P<0.05). A Significant reduction in plasma levels of testosterone in prostate cancer subjects compared with BPH and controls was observed (P<0.001). The plasma levels of androgen receptors were significantly increased in PCa and BPH participants (p<0.05). We observed a positive correlation between ERβ levels and PSA levels in the PCa group (r=0.32, p=0.02). There was a differential expression of AR, ESR1 and ESR2 in the studied group. This study shows hypogonadism and an increased 17β-estradiol, ERβ, and AR levels in subjects with prostate cancer. This data suggests that modulation of these hormones and their receptors may be associated with initiation and progression of prostate cancer and could be valuable in the interpretation of PSA kinetics and stratification of cases after screening.