Effect of testosterone on permeability glycoprotein expression in adult rat testes
Permeability glycoprotein (PGP) is a multidrug resistance 1 (MDR1) transporter and its over-expression protects cancer cells from chemotherapy and makes tumors drug-resistant. Therefore, it is important to understand the regulation of PGP expression in different tissues, including testes. Although PGP is expressed in different cells of the testis, the mechanism of regulation or if it is regulated in the different cell types is not clear. Here we have treated adult male rats with ethane dimethane sulfonate (EDS), a Leydig cell-specific toxicant, to deplete testosterone and investigate the role of testosterone in PGP expression in rat testes. For gene expression analysis, tissues were collected at 6 hr, 15 hr, 24 hr, 5 day and 7 day post-EDS treatment. Luteinizing hormone receptor (LHR) and insulin like peptide-3 (INSL3) are markers of Leydig cells. Quantification of mRNAs for Lhr and Insl3 using real-time PCR was performed to analyze the rate of Leydig cell loss post-EDS treatment. PGP expression was elevated significantly at 15 hr post-EDS and remained 10 fold above at 24 hr, and 7- to 8-fold higher at 5 and 7 day post-EDS. Although EDS treatment leads to testosterone depletion, testosterone replacement had a negligible effect on PGP expression at any of the time points evaluated. From this study, we conclude that PGP expression in rat testes is mostly likely not regulated by testosterone. Thus, PGP expression may be induced by selective chemical insults and these chemical insults may induce a constitutive expression of PGP on a prolonged basis after the primary chemical exposure.