title: Benzo[a]pyrene reduces testosterone production in rat Leydig cells via a direct disturbance of testicular steroidogenic machinery.
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.
authors: Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan, Korea.
authors: Jin-Yong
authors: JY
authors: Chung
authors: Yoon-Jae
authors: YJ
authors: Kim
authors: Ji Young
authors: JY
authors: Kim
authors: Seung Gee
authors: SG
authors: Lee
authors: Ji-Eun
authors: JE
authors: Park
authors: Won Rok
authors: WR
authors: Kim
authors: Yong-Dal
authors: YD
authors: Yoon
authors: Ki Soo
authors: KS
authors: Yoo
authors: Young Hyun
authors: YH
authors: Yoo
authors: Jong-Min
authors: JM
authors: Kim
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D000818:Animals; D017209:Apoptosis; D001564:Benzo(a)pyrene / Q000633:toxicity*; D015153:Blotting, Western / Q000662:veterinary; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000037:antagonists & inhibitors*; D052244:Endocrine Disruptors / Q000633:toxicity*; D004822:Epididymis / Q000187:drug effects / Q000378:metabolism; D020287:In Situ Nick-End Labeling / Q000662:veterinary; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010750:Phosphoproteins / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D013091:Spermatogenesis; D013093:Spermatogonia / Q000187:drug effects* / Q000378:metabolism; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D013739:Testosterone / Q000032:analysis / Q000096:biosynthesis* / Q000097:blood / Q000494:pharmacology; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D052244:Endocrine Disruptors; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D001564:Benzo(a)pyrene; D013739:Testosterone; D015096:3-Hydroxysteroid Dehydrogenases; C477269:3 beta-hydroxy-delta 5-steroid dehydrogenase, rat; D002786:Cholesterol Side-Chain Cleavage Enzyme