Journal Article

Perfluorododecanoic Acid-Induced Steroidogenic Inhibition is Associated with Steroidogenic Acute Regulatory Protein and Reactive Oxygen Species in cAMP-Stimulated Leydig Cells

Zhimin Shi, Yixing Feng, Jianshe Wang, Hongxia Zhang, Lina Ding and Jiayin Dai

in Toxicological Sciences

Volume 114, issue 2, pages 285-294
Published in print April 2010 | ISSN: 1096-6080
Published online January 2010 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfq014
Perfluorododecanoic Acid-Induced Steroidogenic Inhibition is Associated with Steroidogenic Acute Regulatory Protein and Reactive Oxygen Species in cAMP-Stimulated Leydig Cells

More Like This

Show all results sharing these subjects:

  • Medical Toxicology
  • Toxicology (Non-medical)

GO

Show Summary Details

Preview

Perfluorododecanoic acid (PFDoA) can be detected in environmental matrices and human serum and has been shown to inhibit testicular steroidogenesis in rats. However, the mechanisms that are responsible for the toxic effects of PFDoA remain unknown. The aims of this study were to investigate the mechanism of steroidogenesis inhibition by PFDoA and to identify the molecular target of PFDoA in Leydig cells. The effects of PFDoA on steroid synthesis in Leydig cells were assessed by radioimmunoassay. The expression of key genes and proteins in steroid biosynthesis was determined by real-time PCR and Western blot analysis. Reactive oxygen species (ROS) and hydrogen peroxide (H2O2) levels were determined using bioluminescence assays. PFDoA inhibited adenosine 3′,5′-cyclophosphate (cAMP)-stimulated steroidogenesis in mouse Leydig tumor cells (mLTC-1) and primary rat Leydig cells in a dose-dependent manner. However, PFDoA (1–100μM) did not exhibit effects on cell viability and cellular ATP levels in mLTC-1 cells. PFDoA inhibited steroidogenic acute regulatory protein (StAR) promoter activity and StAR expression at the messenger RNA (mRNA) and protein levels but did not affect mRNA levels of peripheral-type benzodiazepine receptor, cholesterol side-chain cleavage enzyme, or 3β-hydroxysteroid dehydrogenase in cAMP-stimulated mLTC-1 cells. PFDoA treatment also resulted in increased levels of mitochondrial ROS and H2O2. After excessive ROS and H2O2 were eliminated in PFDoA-treated mLTC-1 cells by MnTMPyP (a superoxide dismutase analog), progesterone production was partially restored and StAR mRNA and protein levels were partially recovered. These data show that PFDoA inhibits steroidogenesis in cAMP-stimulated Leydig cells by reducing the expression of StAR through a model of action involving oxidative stress.

Keywords: PFDoA; steroidogenesis; StAR; ROS

Journal Article.  6386 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.