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 microg/m(3) in mass weight, 2.27x10(5)/cm(3) in mean number concentration), and medium (26.1+/-0.5 nm, 36.4+/-1.2 microg/m(3), 5.11x10(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+/-0.5 nm, 168.8+/-2.7 microg/m(3), 1.36x10(6)/cm(3)) 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.
Ramdhan
Doni Hikmat
DH
Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Japan.
Ito
Yuki
Y
Yanagiba
Yukie
Y
Yamagishi
Nozomi
N
Hayashi
Yumi
Y
Li
ChunMei
C
Taneda
Shinji
S
Suzuki
Akira K
AK
Watanabe
Gen
G
Taya
Kazuyoshi
K
Kamijima
Michihiro
M
Nakajima
Tamie
T
D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism; D000072467:Cytochrome P450 Family 2; D052244:Endocrine Disruptors; D004958:Estradiol / Q000096:biosynthesis; D013006:Growth Hormone / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D053758:Nanoparticles / Q000633:toxicity*; D010316:Particle Size; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D039181:Steroid 16-alpha-Hydroxylase / Q000378:metabolism; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis*; D001335:Vehicle Emissions / Q000633:toxicity*; D000098682:Steroidogenic Acute Regulatory Protein
D000395:Air Pollutants, Occupational; D002352:Carrier Proteins; D052244:Endocrine Disruptors; D010750:Phosphoproteins; D001335:Vehicle Emissions; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D002784:Cholesterol; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase