title: Effects of polybrominated diphenyl ethers on steroidogenesis in rat Leydig cells.
abstract: BACKGROUND
  Polybrominated diphenyl ethers (PBDEs) are brominated flame retardants that have been defined as major environmental pollutants. While previous studies have found that PBDEs may enhance the levels of sex-steroid hormones, their effects on testosterone secretion from rat Leydig cells are unclear. This study investigated the effects and mechanisms of PBDE-710, a mixture of tetra- and penta-PBDEs, on testosterone biosynthesis in rat Leydig cells.
  
  
  METHODS
  Leydig cells from adult male rats were challenged with different concentrations of PBDE-710 (0.5-15 ng/ml) to evaluate the effects on testosterone steroidogenesis. Concentrations of testosterone and of cAMP and pregnenolone in medium were measured by radioimmunoassay (RIA) and by enzyme-linked immunosorbent assay, respectively. Nuclear translocation of protein kinase A α (PKAα) was determined by immunofluorence assay and western blot assay, and the mRNA expression of steroidogenic acute regulatory protein (StAR) was analyzed by quantitative real-time polymerase chain reaction.
  
  
  RESULTS
  In this in vitro study, PBDE-710 (5 or 15 ng/ml) increased basal testosterone secretion and cAMP production by 3- and 2-fold, respectively. The stimulatory effect was abolished by adenylyl cyclase inhibitor. Enzyme activity of CYP11A1, as determined by the pregnenolone concentration, was stimulated by PBDE-710 treatment. Furthermore, nuclear translocation of PKAα was increased by 20% and StAR gene expression was elevated by 4-fold after PBDE-710 treatment.
  
  
  CONCLUSIONS
  These results suggest that low concentrations of PBDE-710 could stimulate testosterone secretion by acting directly on Leydig cells to activate the cAMP pathway and increase expression of StAR.
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Shih-Pai, Taipei.
authors.forename: Kai-Lee
authors.initials: KL
authors.lastname: Wang
authors.forename: Shih-Min
authors.initials: SM
authors.lastname: Hsia
authors.forename: I-Fang
authors.initials: IF
authors.lastname: Mao
authors.forename: Mei-Lien
authors.initials: ML
authors.lastname: Chen
authors.forename: Shyi-Wu
authors.initials: SW
authors.lastname: Wang
authors.forename: Paulus S
authors.initials: PS
authors.lastname: Wang
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000187:drug effects / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005411:Flame Retardants / Q000494:pharmacology*; D055768:Halogenated Diphenyl Ethers / Q000494:pharmacology*; D066298:In Vitro Techniques; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010750:Phosphoproteins / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000096:biosynthesis*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D006063:Chorionic Gonadotropin; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; C017759:9-(tetrahydro-2-furyl)-adenine; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013739:Testosterone; D002786:Cholesterol Side-Chain Cleavage Enzyme; D017868:Cyclic AMP-Dependent Protein Kinases; D000225:Adenine