Hershberger assay for antiandrogenic effects of phthalates.
The antiandrogenic effects of seven phthalates, di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), butyl benzyl phthalate (BBP), di-isononyl phthalate (DINP), di-isodecyl phthalate (DIDP), di-n-heptyl phthalate (DnHP), and mono-2-ethyhexyl phthalate (MEHP), were investigated by Hershberger assay in castrated male SD rats. An androgen agonist, testosterone (0.4 mg/kg/d), was administered for 10 consecutive days by subcutaneous (s.c.) injection as a positive control. Additionally, 20, 100, or 500 mg/kg body weight (bw)/d of 6 phthalates (DEHP, DBP, BBP, DINP, DIDP, or DnHP) or 10, 50, or 250 mg/kg bw/d of MEHP, the primary metabolite of DEHP, were also administered orally in combination with testosterone (0.4 mg/kg/d, s.c.) for 10 consecutive days, respectively. In the testosterone-treated groups, glans penis, seminal vesicles, ventral prostate, and levator ani/bulbocavernosus muscles (LABC) weights were found to be significantly increased. Ventral prostate weights were significantly decreased in animals treated with DEHP or DBP at doses of 20 mg/kg bw/d or above, 500 mg/kg bw/d DIDP, and 250 mg/kg bw/d MEHP. Seminal vesicles weights were also significantly decreased by DEHP at > 100 mg/kg bw/d, DINP at > 20 mg/kg bw/d, DIDP at 500 mg/kg bw/d, or MEHP at 50 or 250 mg/kg bw/d, respectively. In addition, LABC weights were decreased by DEHP at 500 mg/kg bw/d, DINP at 500 mg/kg bw/d, and MEHP at 50 or 100 mg/kg bw/d. These data suggest that some phthalates possess antiandrogenic activity, and that multiple cross-talk between androgen, estrogen, and steroid hormone receptors occurs.
Lee
Byung Mu
BM
Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, Republic of Korea. bmlee@skku.ac.kr
Koo
Hyun Jung
HJ
D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D001072:Apraxias; D001681:Biological Assay; D052244:Endocrine Disruptors / Q000494:pharmacology*; D008297:Male; D009919:Orchiectomy; D010795:Phthalic Acids / Q000494:pharmacology*; D011467:Prostate / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012669:Seminal Vesicles / Q000187:drug effects*; D013739:Testosterone / Q000037:antagonists & inhibitors*
D000726:Androgen Antagonists; D052244:Endocrine Disruptors; D010795:Phthalic Acids; D013739:Testosterone; C032279:phthalic acid