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.

Bisphenol A disrupts gene expression in human placental trophoblast cells

“…Therefore, our present demonstration of BPA stimulation of aromatase expression may have significant implications for the function of estrogens during pregnancy. Although our present findings are in contrast to those reported previously of decreased aromatase activity and expression in JEG-3 cells [33,35], they are consistent with those of numerous in vitro and in vivo studies [48][49][50][51][52][53][54][55]. For example, BPA exposure has been shown to increase aromatase expression in the rat brain [50,53], ovary [51] and prostate [54].…”

Maternal Transfer of Bisphenol A During Nursing Causes Sperm Impairment in Male Offspring

“…The decrease in anogenital distance in our highest BPA treatment (3000 lg/kg/day) may be explained by reduced available serum testosterone or an increase in aromatase expression and/or activity, as mentioned previously by Quignot et al (2012). There is some evidence for effects of BPA at the androgen receptor (AR) (Vinggaard et al 2008), which may be due the down regulation of 5-areductase expression in mice BPA treated during the development (Castro et al 2013;Liu et al 2015). Reduced 5-a-reductase expression reduces the dihydrotestosterone levels and elevates plasma estradiol levels.…”

Bisphenol A, bisphenol F and bisphenol S affect differently 5α-reductase expression and dopamine–serotonin systems in the prefrontal cortex of juvenile female rats

“…Protein concentration was determined using Bio-Rad DC⨵ assay reagent (BioRad Laboratories) with Protein assay standard II (Bovine serum albumin, Bio-Rad) as the standard. Aliquots of samples were subjected to 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), western blot and antibodies incubation following Castro et al (2013a). Primary antibody concentration was rabbit anti-5α-R2 (Santa Cruz sc-20659), 1:100; rabbit anti-5α-R3 (Novus Biologicals NBP1-69612), 1:1000.…”

“…Our previous findings indicated that adult exposure to BPA decreases the expression of 5α-R isozymes type 1 and type 2 in the prostate of rats (Castro et al, 2013a). In contrast, BPA failed to modify 5α-R expression in the prefrontal cortex (PFC) of adult (Castro et al, 2013b) or juvenile (Castro et al, 2015) male rats.…”