Perfluorododecanoic acid-induced steroidogenic inhibition is associated with steroidogenic acute regulatory protein and reactive oxygen species in cAMP-stimulated Leydig cells

Toxicological Sciences : an Official Journal of the Society of Toxicology
Zhimin ShiJiayin Dai

Abstract

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 (H(2)O(2)) 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 (1-100 microM) 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 recept...Continue Reading

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Citations

Jun 27, 2013·Toxicology Letters·Zhimin ShiJiayin Dai
Apr 11, 2013·Chemical Reviews·Manolis D Tzirakis, Michael Orfanopoulos
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Nov 30, 2018·Chemical Research in Toxicology·Yong ChenRen-Shan Ge

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