Evaluation of anti-androgenic activity of di-(2-ethylhexyl)phthalate.
DEHP is a widely used platiciser in the manufacture of PVC-based materials. It is known to disrupt the reproductive tract development in male rats. We have performed the Hershberger assay with DEHP on an immature castrated rat model to check if DEHP antagonise the testosterone propionate androgenic effect on the accessory sex organs development. DEHP significantly decreased the BC/LA muscles, the prostate, and the seminal vesicles relative weights from 100, 200, and 400 mg/kg bw/day, respectively. DEHP increased the liver relative weight from 100 mg/kg bw/day. A study was also performed on MDA-MB453 cell line stably transfected with pMMTVneo-Luc with DEHP and its major metabolites (MEHP and metabolites VI and IX) to identify anti-androgenic activity. Neither DEHP nor MEHP antagonised DHT activity in the MDA-MB453 transfected cells. In contrast, metabolites VI and IX were anti-androgenic in vitro. DEHP appeared not to be a 5alpha-reductase inhibitor and acted in an independent mechanism from the testicular production in the young rat.
Stroheker
Thomas
T
UMR 1234 Toxicologie Alimentaire, University of Burgundy/INRA, 1 Esplanade Erasme, 21000 Dijon, France.
Cabaton
Nicolas
N
Nourdin
Gorian
G
Régnier
Jean-François
JF
Lhuguenot
Jean-Claude
JC
Chagnon
Marie-Christine
MC
D000726:Androgen Antagonists / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D045744:Cell Line, Tumor; D004051:Diethylhexyl Phthalate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity*; D013196:Dihydrotestosterone / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005837:Genitalia, Male / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008156:Luciferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D010795:Phthalic Acids / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D010968:Plasticizers / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D043343:Testosterone Propionate / Q000037:antagonists & inhibitors
D000726:Androgen Antagonists; D010795:Phthalic Acids; D010968:Plasticizers; C479069:mono(2-ethyl-5-hydroxyhexyl) phthalate; D013196:Dihydrotestosterone; C080276:mono(2-ethyl-5-oxohexyl)phthalate; D004051:Diethylhexyl Phthalate; D008156:Luciferases; C016599:mono-(2-ethylhexyl)phthalate; D043343:Testosterone Propionate