Benzo[a]pyrene reduces testosterone production in rat leydig cells via a direct disturbance of testicular steroidogenic machinery

Jin Yong Chung, Yoon Jae Kim, Ji Young Kim, Seung Gee Lee, Ji Eun Park, Won Rok Kim, Yong Dal Yoon, Ki Soo Yoo, Young Hyun Yoo, Jong Min Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon (PAH), is a ubiquitous environmental pollutant that is currently suspected of being an endocrine disruptor. The testis is an important target for PAHs, yet insufficient attention has been paid to their effects on steroidogenesis in Leydig cells. Objective: We hypothesized that long-term exposure to low concentrations of B[a]P might disrupt testosterone production in Leydig cells via an alteration of steroidogenic proteins. Results: Oral exposure to B[a]P reduced serum and intratesticular fluid testosterone levels in rats. However, we did not observe serious testicular atrophy or azoospermia, although spermatogonial apoptosis was significantly increased. Compared with control cells, Leydig cells primed with B[a]P in vivo produced less testosterone in response to human chorionic gonadotropin (hCG) or dibutyl cyclic adenosine monophosphate in vitro. Of note, the reduction of testosterone levels was accompanied by decreased expression of steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD), as well as increased levels of cytochrome P450 side chain cleavage (P450scc), in Leydig cells. The up-regulation of P450scc expression after exposure to B[a]P appears to be associated with a compensatory mechanism for producing the maximum amount of pregnenolone with the minimum amount of transported cholesterol by StAR; the down-regulation of 3β-HSD may occur because B[a]P can negatively target 3β-HSD, which is required for testosterone production. Conclusions: B[a]P exposure can decrease epididymal sperm quality, possibly by disturbing testosterone levels, and StAR may be a major steroidogenic protein that is targeted by B[a]P or other PAHs.

Original languageEnglish (US)
Pages (from-to)1059-1074
Number of pages16
JournalEnvironmental health perspectives
Volume119
Issue number11
DOIs
StatePublished - Nov 2011
Externally publishedYes

Keywords

  • Benzo[a]Pyrene
  • Endocrine disruptor
  • Epididymal sperm
  • Leydig cells
  • Steroidogenesis
  • Testosterone

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

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