TY - JOUR
T1 - Nanoparticle-rich diesel exhaust may disrupt testosterone biosynthesis and metabolism via growth hormone
AU - Ramdhan, Doni Hikmat
AU - Ito, Yuki
AU - Yanagiba, Yukie
AU - Yamagishi, Nozomi
AU - Hayashi, Yumi
AU - Li, Chun Mei
AU - Taneda, Shinji
AU - Suzuki, Akira K.
AU - Watanabe, Gen
AU - Taya, Kazuyoshi
AU - Kamijima, Michihiro
AU - Nakajima, Tamie
N1 - Funding Information:
This study was supported in part by Grants-in-Aid from the Ministry of the Environment, Japan (2007, 2008).
PY - 2009/12/15
Y1 - 2009/12/15
N2 - 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.
AB - 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.
KW - Growth hormone receptor
KW - Nanoparticle-rich diesel exhaust
KW - P450scc
KW - StAR
KW - Testosterone biosynthesis
UR - http://www.scopus.com/inward/record.url?scp=70449535625&partnerID=8YFLogxK
U2 - 10.1016/j.toxlet.2009.08.013
DO - 10.1016/j.toxlet.2009.08.013
M3 - Article
C2 - 19699283
AN - SCOPUS:70449535625
SN - 0378-4274
VL - 191
SP - 103
EP - 108
JO - Toxicology Letters
JF - Toxicology Letters
IS - 2-3
ER -