The xenoestrogen bisphenol A in the Hershberger assay: Androgen receptor regulation and morphometrical reactions indicate no major effects

We evaluated androgen-like effects of bisphenol A (BPA) using orchiectomized Wistar rats. Animals were treated p.o. either with vehicle or with 3, 50, 200, 500 mg/kg bw/day BPA (n = 13) for 7 days. One group was treated s.c. with 1 mg/kg bw/day testosterone propionate (TP). Flutamide (FL) (3 mg/kg bw/day, p.o.) was used to antagonize androgen effects of the suprapharmacological dose (500 mg/kg bw/day) of BPA. Androgen-like effects of BPA on prostates and seminal vesicles were assessed by the Hershberger assay, densitometric analysis of androgen receptor (AR) immunoreactivity, cell proliferation-index and a morphometric analysis. Absolute weights of prostates and seminal vesicles were not increased by BPA, whereas the relative weights were increased at higher doses of BPA, most likely due to a decrease in body weight. Staining intensity for AR immunoreactivity was increased at low but not at higher doses of BPA in comparison to the orchiectomized rats. BPA at all doses tested did not cause an increase of the cell proliferation-index. Epithelial height and glandular luminal area were increased by low doses of BPA, whereas higher doses caused a decrease of these parameters. The data provide evidence that BPA does not exert major androgenic effects.