Nanoparticle-rich diesel exhaust may disrupt testosterone biosynthesis and metabolism via growth hormone

We previously reported that exposure to low (22.5 ± 0.2 nm in diameter, 15.4 ± 1.0 μg/m3 in mass weight, 2.27 × 105/cm3 in mean number concentration), and medium (26.1 ± 0.5 nm, 36.4 ± 1.2 μg/m3, 5.11 × 105/cm3) 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 ± 0.5 nm, 168.8 ± 2.7 μg/m3, 1.36 × 106/cm3) did not. 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.