6533b7d3fe1ef96bd12609c0
RESEARCH PRODUCT
Evaluation of anti-androgenic activity of di-(2-ethylhexyl)phthalate
Jean-claude LhuguenotMarie-christine ChagnonThomas StrohekerGorian NourdinNicolas CabatonJean-françois Regniersubject
Testosterone propionateMalemedicine.medical_specialtyendocrine systemMDA-MB453 TRANSFECTED CELL LINEmedicine.drug_classMetabolitePhthalic AcidsMONO-(2-ETHYLHEXYL1)PHTHALATE010501 environmental sciencesGenitalia MaleToxicologyAntiandrogen01 natural sciences03 medical and health scienceschemistry.chemical_compoundProstatePlasticizersInternal medicineCell Line TumorDiethylhexyl PhthalatemedicineAnimalsRats WistarLuciferases030304 developmental biology0105 earth and related environmental sciences0303 health sciencesDose-Response Relationship DrugPhthalateMONO-(2-ETHYL-5-HYDROXYLHEXYL)PHTHALATEBiological activityAndrogen AntagonistsDihydrotestosteroneDrug SynergismOrgan SizeMETABOLITES MONO-(2-ETHYL-5-OXOHEXYL1)PHTHALATEIn vitroRatsTestosterone PropionateEndocrinologymedicine.anatomical_structurechemistryLiverCell culture[SDV.TOX]Life Sciences [q-bio]/ToxicologyHERSHBERGER ASSAYDI-(2-ETHYLHEXYL1)PHTHALATEOrchiectomydescription
International audience; 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 5α-reductase inhibitor and acted in an independent mechanism from the testicular production in the young rat.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2005-01-01 |