Bisphenol A exposure during adulthood alters expression of aromatase and 5α-reductase isozymes in rat prostate.

Abstract

The high incidence of prostate cancer (PCa) and benign prostatic hypertrophy (BPH) in elderly men is a cause of increasing public health concern. In recent years, various environmental endocrine disruptors, such as bisphenol A (BPA), have been shown to disrupt sexual organs, including the prostate gland. However, the mechanisms underlying these effects remain unclear. Because androgens and estrogens are important factors in prostate physiopathology, our objective was to examine in rat ventral prostate the effects of adult exposure to BPA on 5α-Reductase isozymes (5α-R types 1, 2, and 3) and aromatase, key enzymes in the biosynthesis of dihydrotestosterone and estradiol, respectively. Adult rats were subcutaneously injected for four days with BPA (25, 50, 300, or 600 µg/Kg/d) dissolved in vehicle. Quantitative RT-PCR, western blot and immunohistochemical analyses showed lower mRNA and protein levels of 5α-R1 and 5α-R2 in BPA-treated groups versus controls but higher mRNA levels of 5α-R3, recently proposed as a biomarker of malignancy. However, BPA treatment augmented mRNA and protein levels of aromatase, whose increase has been described in prostate diseases. BPA-treated rats also evidenced a higher plasma estradiol/testosterone ratio, which is associated with prostate disease. Our results may offer new insights into the role of BPA in the development of prostate disease and may be of great value for studying the prostate disease risk associated with exposure to BPA in adulthood.