title: Xenoandrogenic activity in serum differs across European and Inuit populations.
abstract: BACKGROUND
  Animal and in vitro studies have indicated that human male reproductive disorders can arise as a result of disrupted androgen receptor (AR) signalling by persistent organic pollutants (POPs). Our aim in the present study was to compare serum xenoandrogenic activity between study groups with different POP exposures and to evaluate correlations to the POP proxy markers 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE).
  
  
  METHODS
  We determined xenoandrogenic activity in the serum fraction containing the lipophilic POPs but free of endogenous hormones. Adult male serum (n = 261) from Greenland, Sweden, Warsaw (Poland), and Kharkiv (Ukraine) was analyzed. Xenoandrogenic activity was determined as the effect of serum extract alone (XAR) and in the presence of the synthetic AR agonist R1881 (XARcomp) on AR transactivated luciferase activity.
  
  
  RESULTS
  The study groups differed significantly with respect to XARcomp activity, which was increased in the Inuits and decreased in the European study groups; we observed no difference for XAR activity. We found the highest level of the AR antagonist p,p'-DDE in Kharkiv, and accordingly, this study group showed the highest percent of serum samples with decreased XARcomp activities. Furthermore, the percentage of serum samples with decreased XARcomp activities followed the p,p'-DDE serum level for the European study groups. No correlations between serum XAR or XARcomp activities and the two POP markers were revealed.
  
  
  CONCLUSIONS
  The differences in XARcomp serum activity between the study groups suggest differences in chemical exposure profiles, genetics, and/or lifestyle factors.
authors.affiliation: Department of Environmental and Occupational Medicine, Institute of Public Health, University of Aarhus, Aarhus, Denmark.
authors.forename: Tanja
authors.initials: T
authors.lastname: Krüger
authors.forename: Philip S
authors.initials: PS
authors.lastname: Hjelmborg
authors.forename: Bo A G
authors.initials: BA
authors.lastname: Jönsson
authors.forename: Lars
authors.initials: L
authors.lastname: Hagmar
authors.forename: Aleksander
authors.initials: A
authors.lastname: Giwercman
authors.forename: Gian-Carlo
authors.initials: GC
authors.lastname: Manicardi
authors.forename: Davide
authors.initials: D
authors.lastname: Bizzaro
authors.forename: Marcello
authors.initials: M
authors.lastname: Spanò
authors.forename: Anna
authors.initials: A
authors.lastname: Rignell-Hydbom
authors.forename: Henning S
authors.initials: HS
authors.lastname: Pedersen
authors.forename: Gunnar
authors.initials: G
authors.lastname: Toft
authors.forename: Jens Peter
authors.initials: JP
authors.lastname: Bonde
authors.forename: Eva C
authors.initials: EC
authors.lastname: Bonefeld-Jørgensen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000728:Androgens / Q000097:blood / Q000633:toxicity; D003633:Dichlorodiphenyl Dichloroethylene / Q000097:blood / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000097:blood / Q000633:toxicity*; D004781:Environmental Exposure / Q000009:adverse effects*; D004785:Environmental Pollutants / Q000097:blood / Q000633:toxicity*; D005060:Europe; D006801:Humans; D004930:Inuit; D008019:Life Style; D008156:Luciferases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011078:Polychlorinated Biphenyls / Q000097:blood / Q000633:toxicity*; D011944:Receptors, Androgen / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction; D044465:White People
chemical_list: D000728:Androgens; D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D011944:Receptors, Androgen; D003633:Dichlorodiphenyl Dichloroethylene; D011078:Polychlorinated Biphenyls; D008156:Luciferases; C014024:2,4,5,2',4',5'-hexachlorobiphenyl