Effects of Environmental Antiandrogenic Chemicals on Expression of Androgen-Responsive Genes in Rat Prostate Lobes

Abstract

Rat prostate, which is usually used in the Hershberger assay for evaluating the antiandrogenic activity of environmental chemicals in vivo ,h as ac omplex structure consisting 4 lobes, i.e. ,t he ventral prostate (VP), lateral prostate (LP), dorsal prostate (DP) and anterior prostate (AP). The VP is considered to have no counterpart in primates, while the LP and DP are histologically similar to human prostate. However, the Hershberger assay focuses on the VP, not the other lobes. Moreover, there are few other methods for assessment of antiandrogenic activity in vivo .W et herefore investigated androgen-responsive genes in the DP, as well as VP, following treatment with environmental chemicals reported to be androgen antagonists. Male castrated F344 rats were treated with testosterone (0.5 mg·kg −1 ·day −1 )a lone or together with flutamide (6 mg·kg −1 ·day −1 )a s ar eference antiandrogen or fenthion (25 mg·kg −1 ·day −1 )o r fenitrothion (25 mg·kg −1 ·day −1 )o r 2,4,4 � -trihydroxybenzophenone (2,4,4 � -triOHBP) (300 mg·kg −1 ·day −1 )f or 7d ays. Testosterone significantly increased the expression of kallikrein S3, cystatinrelated protein-1 (CRP-1) and prostatein C3 mRNAs in the VP, and prostate secretory protein of 94 amino acids (PSP94) mRNA, but not stem cell growth factor (SCGF) mRNA, in the DP. Coadministration of flutamide blocked the testosterone-induced increases of all three mRNAs in the VP, but not that of PSP94 mRNA in the DP. Coadministration of fenitrothion significantly reduced the testosterone-induced increase of kallikrein S3 mRNA, while fenthion significantly increased the testosterone-induced increase of PSP94 mRNA. 2,4,4 � -TriOH-BP significantly increased the testosterone-induced increases of CRP-1 and prostatein C3 mRNAs. These results indicate that the effects of environmental chemicals on the prostate are very complex. The Hershberger assay alone appears to be inadequate for risk assessment, and it may be useful to employ androgen-responsive genes as additional markers.