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

Doni Hikmat Ramdhan, Yuki Ito, Yukie Yanagiba, Nozomi Yamagishi, Yumi Hayashi, Chun Mei Li, Shinji Taneda, Akira K. Suzuki, Gen Watanabe, Kazuyoshi Taya, Michihiro Kamijima, Tamie Nakajima

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)103-108
Number of pages6
JournalToxicology Letters
Volume191
Issue number2-3
DOIs
Publication statusPublished - 15 Dec 2009

Keywords

  • Growth hormone receptor
  • Nanoparticle-rich diesel exhaust
  • P450scc
  • StAR
  • Testosterone biosynthesis

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