Internal dose-effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in gonadotropin-primed weanling rat model.
Single sc injection of 5 IU equine chorionic gonadotropin (eCG) induces ovulation in weanling female rats 3 days later. It has been shown that treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) 24 h before eCG injection reduces eCG-stimulated ovarian hypertrophy and inhibits ovulation. The present study intended to compare internal dose-effects of TCDD between these endpoints and representative endpoints for TCDD toxicity, such as weights of the liver and thymus, in weanling female rats given orally 0, 1, 4 or 16 microg/kg TCDD 24 h before eCG injection on postnatal day 25. Measurement of plasma TCDD concentrations by ELISA at 6, 72 and 96 h after TCDD revealed that significant levels of TCDD were maintained in systemic circulation until 96 h (on the day of induced ovulation) with the highest level at 6 h after TCDD treatment. Ovarian TCDD concentrations varied similarly and tended to be higher than those in the thymus at all time points, whereas hepatic concentrations of TCDD were the highest among the tissues. Although > or = 4 microg/kg TCDD affected the weights of the thymus and liver, no differences were observed in ovarian weights at any time point or in ovulation between corn oil-treated and TCDD-treated groups. Furthermore, ovarian levels of representative mRNAs in follicles were not affected by TCDD treatment. Since TCDD increased the amount of cytochrome P450 1A1 mRNA in the ovary, the administered TCDD stimulated the aryl hydrocarbon receptor-signaling pathway. From these results, we concluded that thymus weights of weanling female rats responded to TCDD at a lower internal dose as compared with that ovarian hypertrophy and follicular growth from early antral stage to ovulation would respond to.
Shirota
Mariko
M
Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano-shi, Kanagawa 257-8523, Japan. shirota.m@fdsc.or.jp
Kaneko
Toyozo
T
Okuyama
Mitsunobu
M
Sakurada
Yosuke
Y
Shirota
Kinji
K
Matsuki
Yasuhiko
Y
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004785:Environmental Pollutants / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity; D005260:Female; D006064:Gonadotropins, Equine / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects* / Q000502:physiology; D010060:Ovulation / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013950:Thymus Gland / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D014599:Uterus / Q000187:drug effects / Q000254:growth & development
D004785:Environmental Pollutants; D006064:Gonadotropins, Equine; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D019363:Cytochrome P-450 CYP1A1