title: Nanoparticle-rich diesel exhaust may disrupt testosterone biosynthesis and metabolism via growth hormone.
abstract: 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.
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Japan.
authors.forename: Doni Hikmat
authors.initials: DH
authors.lastname: Ramdhan
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ito
authors.forename: Yukie
authors.initials: Y
authors.lastname: Yanagiba
authors.forename: Nozomi
authors.initials: N
authors.lastname: Yamagishi
authors.forename: Yumi
authors.initials: Y
authors.lastname: Hayashi
authors.forename: ChunMei
authors.initials: C
authors.lastname: Li
authors.forename: Shinji
authors.initials: S
authors.lastname: Taneda
authors.forename: Akira K
authors.initials: AK
authors.lastname: Suzuki
authors.forename: Gen
authors.initials: G
authors.lastname: Watanabe
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Taya
authors.forename: Michihiro
authors.initials: M
authors.lastname: Kamijima
authors.forename: Tamie
authors.initials: T
authors.lastname: Nakajima
mesh_terms: 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
chemical_list: 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