Induction of uterine calbindin-D9k through an estrogen receptor-dependent pathway following single injection with xenobiotic agents in immature rats.
Various environmental chemicals, both natural and synthetic, are believed to act as endocrine disruptors (EDs) in mammals. In this study, a new in vivo model of immature rats was used to explore the induction of calbindin-D9k (CaBP-9k) following a single injection of EDs. In a time-dependent experiment, immature rats at postnatal day 16 were treated with high doses (600 mg/kg body weight [BW]) of 4-tert-octyphenol (OP), p-nonylphenol (NP), or bisphenol A (BPA), and euthanized at different time points (3, 6, 12, 24, or 48 h). For a dose-dependent study, immature rats were given different doses (200, 400, or 600 mg/kg BW) and euthanized at 24 h after injection. After treatment with these EDs, the effects on CaBP-9k mRNA and protein were examined by Northern and Western blot analyses, respectively. An anti-estrogen, ICI 182,780, was employed to examine the potential involvement of estrogen receptor (ER) in the induction of estrogen receptor-mediated physiologic responses in vivo. A single treatment with each of the chemicals, at 600 mg/kg BW, resulted in a significant increase in the expression of CaBP-9k mRNA and protein 24 h after injection. In addition, treatment with OP, NP, or BPA resulted in a positive uterotrophic response. Cotreatment with the ER antagonist ICI 182,780 completely prevented the ED-induced uterine weight gain. Taken together, these results demonstrate that a single injection of OP, NP, or BPA results in an increase of CaBP-9k mRNA and protein via an ER-dependent pathway in the uterus of immature rats. This new model may be important to elucidate the mechanism of action of xenoestrogens on estrogen-sensitive tissue.
Dang
Vu Hoang
VH
Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Choi
Kyung-Chul
KC
Hyun
Sang-Hwan
SH
Jeung
Eui-Bae
EB
D000818:Animals; D001559:Benzhydryl Compounds; D064026:Calbindins; D052244:Endocrine Disruptors / Q000633:toxicity; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000633:toxicity; D005260:Female; D000077267:Fulvestrant; D007279:Injections, Subcutaneous; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000096:biosynthesis* / Q000235:genetics; D014599:Uterus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D015262:Xenobiotics / Q000633:toxicity; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D064026:Calbindins; D052244:Endocrine Disruptors; D004958:Estradiol; D004965:Estrogen Antagonists; D004968:Estrogens, Non-Steroidal; D000077267:Fulvestrant; D010636:Phenols; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D064030:S100 Calcium Binding Protein G; D015262:Xenobiotics; C576508:S100g protein, rat; C025256:nonylphenol; C105260:4-tert-octylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds