No androgenic/anti-androgenic effects of bisphenol-A in Hershberger assay using immature castrated rats.
Several studies have demonstrated that bisphenol A (BPA) exhibited weak estrogenic activity in the 3-day uterotrophic assay using ovariectomized (OVX) and immature rats (Toxicol. Lett. 115 (2000) 231; Regul. Toxicol. Pharmacol. 32 (2000) 118; J. Toxicol. Sci. 26 (2001) 111) and BPA also possessed anti-androgenic activity in in vitro yeast based assays (J. Endocrinol. 158 (1998) 327). To investigate anti-androgenic effects of BPA. a rodent Hershberger assay was carried out using immature Sprague-Dawley male rats. An androgen agonist, testosterone (0.4 mg/kg per day), was administered for 7 consecutive days by subcutaneous (s.c.) injection as a positive control. Additionally, a pure androgen antagonist, flutamide (1, 5. 10 mg/kg per day. oral) was co-administered with testosterone (0.4 mg/kg per day s.c.). BPA was also administered orally with or without testosterone (0.4 mg/kg per day, s.c.) for 7 consecutive days. In the testosterone treated groups, glans penis, seminal vesicles, ventral prostate, and levator ani plus bulbocavernosus muscles (LABC) weights were significantly increased compared with control. However. flulamide dose-dependently inhibited the testosterone-induced re-growth of seminal vesicles, ventral prostate, and LABC, with a significant decrease at flutamide 1.0 mg/kg and above (P<0.05). Serum LH levels were also significantly increased (5 mg/kg and above, P<0.05), but no changes in serum testosterone levels. In contrast, BPA had no effects on the re-growth of seminal vesicles, ventral prostate and LABC induced by testosterone, and no significant differences were observed in serum LH and testosterone levels. In summary, the Hershberger assay could be a sensitive method for detecting androgenic or anti-androgenic chemicals, but BPA did not exhibit any androgenic or anti-androgenic activities in Hershberger assay.
Kim
Hyung Sik
HS
Reproductive and Developmental Toxicology Division, Department of Toxicology, National Institute of Toxicological Research, Korea Food and Drug Administration, 5 Nokbun-dong, Eunpyung-ku, 122-704, Seoul, South Korea.
Han
Soon Young
SY
Kim
Tae Sung
TS
Kwack
Seung Jun
SJ
Lee
Rhee Da
RD
Kim
In Young
IY
Seok
Ji-Hyun
JH
Lee
Byung Mu
BM
Yoo
Sun Dong
SD
Park
Kui Lea
KL
D000726:Androgen Antagonists / Q000378:metabolism*; D000818:Animals; D001559:Benzhydryl Compounds; D001835:Body Weight / Q000187:drug effects; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005485:Flutamide / Q000378:metabolism / Q000494:pharmacology; D005837:Genitalia, Male / Q000033:anatomy & histology / Q000187:drug effects; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D013739:Testosterone / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D000098826:Bisphenol A Compounds
D000726:Androgen Antagonists; D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal; D005485:Flutamide; D007986:Luteinizing Hormone; D010636:Phenols; D013739:Testosterone; C006780:bisphenol A; D000098826:Bisphenol A Compounds