In vivo estrogenic potential of 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene, an active metabolite of bisphenol A, in uterus of ovariectomized rat.
4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), an active metabolite of bisphenol A (BPA), has more potent estrogenic activity than BPA in vitro, but its activity in vivo is not established. Here, we examined in vivo estrogenic activity of MBP by means of uterotrophic assay in ovariectomized (OVX) female rats. MBP exhibited dose-dependent estrogenic activity, as evaluated in terms of effects on uterus weight, uterine luminal epithelial cell height and myometrium thickness. The highest concentration of MBP (10 mg/kg/day) completely reversed the changes caused by OVX, and its activity was equivalent to that of 5 microg/kg/day 17beta-estradiol (E2). We also investigated the effects of MBP on transcription of several estrogen-related genes. The changes of mRNA levels of estrogen receptors alpha and beta, c-fos and insulin-like growth factor 1 in MBP-treated OVX rats were qualitatively similar to those in E2-treated rats. BPA did not show any significant effect on OVX rat in these conditions. This study is the first to demonstrate that MBP, an active metabolite of BPA, has potent in vivo estrogenic activity, being about 500-fold more potent than BPA in OVX rats.
Okuda
Katsuhiro
K
Faculty of Pharmaceutical Sciences, Hiroshima International University, Kure, Hiroshima 737-0112, Japan.
Takiguchi
Masufumi
M
Yoshihara
Shin'ichi
S
D000818:Animals; D001559:Benzhydryl Compounds; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000633:toxicity*; D005260:Female; D009215:Myometrium / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D010636:Phenols / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004967:Estrogens; D010636:Phenols; C504750:4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene; C006780:bisphenol A; D000098826:Bisphenol A Compounds