title: Bisphenol A, bisphenol F and bisphenol S affect differently 5α-reductase expression and dopamine-serotonin systems in the prefrontal cortex of juvenile female rats.
abstract: BACKGROUND
  Early-life exposure to the endocrine disruptor bisphenol A (BPA) affects brain function and behavior, which might be attributed to its interference with hormonal steroid signaling and/or neurotransmitter systems. Alternatively, the use of structural analogs of BPA, mainly bisphenol F (BPF) and bisphenol S (BPS), has increased recently. However, limited in vivo toxicity data exist.
  
  
  OBJECTIVE
  We investigated the effects of BPA, BPF and BPS on 5α-reductase (5α-R), a key enzyme involved in neurosteroidogenesis, as well as on dopamine (DA)- and serotonin (5-HT)-related genes, in the prefrontal cortex (PFC) of juvenile female rats.
  
  
  METHODS
  Gestating Wistar rats were treated with either vehicle or 10 μg/kg/day of BPA, BPF or BPS from gestational day 12 to parturition. Then, female pups were exposed from postnatal day 1 through day 21 (PND21), when they were euthanized and RT-PCR, western blot and quantitative PCR-array experiments were performed.
  
  
  RESULTS
  BPA decreased 5α-R2 and 5α-R3 mRNA and protein levels, while both BPF and BPS decreased 5α-R3 mRNA levels in PFC at PND21. Further, BPA, BPF and BPS significantly altered, respectively, the transcription of 25, 56 and 24 genes out of the 84 DA and 5-HT-related genes assayed. Of particular interest was the strong induction by all these bisphenols of Cyp2d4, implicated in corticosteroids synthesis.
  
  
  CONCLUSIONS
  Our results demonstrate for the first time that BPA, BPF and BPS differentially affect 5α-R and genes related to DA/5-HT systems in the female PFC. In vivo evidence of the potential adverse effects of BPF and BPS in the brain of mammals is provided in this work, raising questions about the safety of these chemicals as substitutes for BPA.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Granada, Avda. de Madrid s/n, 18012 Granada, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Castro
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Granada, Avda. de Madrid s/n, 18012 Granada, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Sánchez
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Granada, Avda. de Madrid s/n, 18012 Granada, Spain; Institute of Neurosciences, Faculty of Medicine, University of Granada, Granada, Spain. Electronic address: torrespi@ugr.es.
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Torres
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Granada, Avda. de Madrid s/n, 18012 Granada, Spain; Institute of Neurosciences, Faculty of Medicine, University of Granada, Granada, Spain. Electronic address: esortega@ugr.es.
authors.forename: Esperanza
authors.initials: E
authors.lastname: Ortega
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D042944:Cholestenone 5 alpha-Reductase / Q000235:genetics / Q000378:metabolism*; D004298:Dopamine; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D012701:Serotonin; D013450:Sulfones / Q000494:pharmacology*; D000098831:Bisphenol S Compounds; D000098833:Bisphenol F Compounds; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D042944:Cholestenone 5 alpha-Reductase; D004298:Dopamine; D007527:Isoenzymes; D010636:Phenols; D012333:RNA, Messenger; D012701:Serotonin; D013450:Sulfones; C543008:bisphenol S; D000098831:Bisphenol S Compounds; C047971:2,4'-bisphenol F; D000098833:Bisphenol F Compounds; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: 5α-reductase; BPA-analogs; Bisphenol A; Dopamine; Serotonin