Oxidative stress and phthalate-induced down-regulation of steroidogenesis in MA-10 Leydig cells

Liang Zhou, Matthew C. Beattie, Chieh Yin Lin, June Liu, Kassim Traore, Vassilios Papadopoulos, Barry R. Zirkin, Haolin Chen

Research output: Contribution to journalArticlepeer-review

Abstract

Previous studies have shown that phthalate exposure can suppress steroidogenesis. However, the affected components of the steroidogenic pathway, and the mechanisms involved, remain uncertain. We show that incubating MA-10 Leydig cells with mono-(2-ethylhexyl) phthalate (MEHP) resulted in reductions in luteinizing hormone (LH)-stimulated cAMP and progesterone productions. cAMP did not decrease in response to MEHP when the cells were incubated with cholera toxin or forskolin. Incubation of MEHP-treated cells with dibutyryl-cAMP, 22-hydroxycholesterol or pregnenolone inhibited the reductions in progesterone. Increased levels of reactive oxygen species (ROS) occurred in response to MEHP. In cells in which intracellular glutathione was depleted by buthionine sulfoximine pretreatment, the increases in ROS and decreases in progesterone in response to MEHP treatment were exacerbated. These results indicate that MEHP inhibits MA-10 Leydig cell steroidogenesis by targeting LH-stimulated cAMP production and cholesterol transport, and that a likely mechanism by which MEHP acts is through increased oxidative stress.

Original languageEnglish (US)
Pages (from-to)95-101
Number of pages7
JournalReproductive Toxicology
Volume42
DOIs
StatePublished - Dec 1 2013

Keywords

  • Leydig cell
  • MEHP
  • Oxidative stress
  • Phthalate
  • Steroidogenesis

ASJC Scopus subject areas

  • Toxicology

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