We previously reported that exposure to low (22.5 +/- 02 nm in diameter, 154 +/- 10 mu g/m(3) in mass weight, 227 x 10(5)/cm(3) in mean number concentration). and medium (26.1 +/- 05 nm, 364 +/- 12 mu g/m(3). 511 x 10(5)/cm(3)) concentrations of nanoparticle-rich diesel exhaust (NR-DE) for 1 and 2 months (5 h/day, 5 days/week) significantly increased plasma testosterone in male Fischer 344 rats, whereas exposure to a high concentration (27.1 +/- 05 nm, 168.8 +/- 2.7 mu g/m(3), 1.36 x 10(6)/cm(3)) did riot The present study attempts to clarify the mechanism of this elevation. Low and medium exposures to NR-DE for 1 and 2 months significantly increased steroidogenic acute regulatory protein (StAR)- and cytochrome P450 side-chain cleavage (P450scc)-mRNA and their protein expressions in the testis of rats. in which the elevation pattern was very similar to that of plasma testosterone levels. Interestingly, both exposure levels for 1 month significantly increased growth hormone (GH) receptor expression in the testis, and low exposure also increased testicular insulin-like growth factor I-mRNA levels and hepatic microsomal cytochrome P450 2C11-mRNA and their protein levels in rats These two factors are thought to be related to growth hormone secretion. Disruption of testosterone biosynthesis by NR-DE exposure may be a mode of action for reproductive toxicity. which may. in part, be regulated by increasing StAR and P450scc expressions via GH signalling. (C) 2009 Elsevier Ireland Ltd. All rights reserved.