title: Effects of monobutyl phthalate on steroidogenesis through steroidogenic acute regulatory protein regulated by transcription factors in mouse Leydig tumor cells.
abstract: OBJECTIVE
  Dibutyl phthalate (DBP) is one of the most widely used phthalate esters, and it is ubiquitous in the environment. DBP and its major metabolite, monobutyl phthalate (MBP), change steroid biosynthesis and impair male reproductive function. However, the regulatory mechanism underlying the steroid biosynthesis disruption by MBP is still unclear.
  
  
  METHODS
  We analyzed the progesterone production, steroidogenic acute regulatory protein (StAR) mRNA, protein expression, and DNA-binding affinity of transcription factors (SF-1 and GATA-4).
  
  
  RESULTS
  Our results reveal that MBP inhibited progesterone production. At the same time, StAR mRNA and protein were decreased after MBP exposure. Furthermore, electrophoretic mobility shift assay showed that DNA-binding affinity of transcription factors (SF-1 and GATA-4) was decreased in a dose-dependent manner after MBP treatments. Western blot tests next confirmed that protein of SF-1 was decreased, but GATA-4 protein was unchanged. However, phosphorylated GATA-4 protein was decreased with 800 μM of MBP.
  
  
  CONCLUSIONS
  This study reveals an important and novel mechanism whereby SF-1 and GATA-4 may regulate StAR during MBP-induced steroidogenesis disruption.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Hu
authors.forename: C
authors.initials: C
authors.lastname: Dong
authors.forename: M
authors.initials: M
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: A
authors.initials: A
authors.lastname: Gu
authors.forename: Y
authors.initials: Y
authors.lastname: Xia
authors.forename: H
authors.initials: H
authors.lastname: Sun
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D050991:GATA4 Transcription Factor / Q000378:metabolism; D007984:Leydig Cell Tumor / Q000378:metabolism*; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism*; D010795:Phthalic Acids / Q000494:pharmacology*; D054339:Steroidogenic Factor 1 / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; D010750:Phosphoproteins; D010795:Phthalic Acids; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; D000098682:Steroidogenic Acute Regulatory Protein; C028577:monobutyl phthalate