[Antiestrogenic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the gene expression of insulin-like growth factors family in osteoblast cells].
OBJECTIVE
To investigate the antiestrogenic effect of environment teratogen on the gene expression of insulin-like growth factors (IGFs) family in osteoblast cells during rat skeleton development.


METHODS
The fetal rat models with congenital skeleton malformation were constructed by treating 20 female Wistar rats with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on pregnant day 10. The MC-3T3-E1 cells were cultured with estrogen, TCDD, or a combination of the two chemicals for 24 hours. The IGF-II and IGFBP-6 mRNA levels in rat calvaria bone tissue and MC-3T3-E1 cells were detected by reverse transcription-polymerase chain reaction. Flow cytometer was used to determine the cell proliferation.


RESULTS
TCDD at the concentration of 5-15 microg/kg induced developmental skeleton defect of fetal rat, and the effect was dose-dependent. The expression of IGF-II mRNA gene was enhanced by estrogen in rat calvaria bone tissue and MC-3T3-E1 cells, whereas IGFBP-6 mRNA was decreased. Estrogen increased the cell proliferation in MC-3T3-E1 cells. TCDD, however, inhibited the effect of estrogen on regulation of IGF-II gene and IGFBP-6 gene as well as MC-3T3-E1 cell proliferation.


CONCLUSIONS
These findings provide the evidence that TCDD can induce congenital fetal skeleton malformation under the condition of high estrogen level in pregnant Wistar rats. TCDD has antiestrogenic effect and hence exerts negative influence on the osteoblast cells through target IGF-II and IGFBP-6 of IGFs family.
Guo
Lei
L
Department of Orthopedic Surgery, the First Clinical College, China Medical University, Shenyang, Liaoning, PR China.
Zhao
Yan-yan
YY
Dong
Ling-yue
LY
Ding
Qian
Q
Sun
Kai-lai
KL
Ji
Shi-jun
SJ
Wang
Lu-zeng
LZ
D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities; D004305:Dose-Response Relationship, Drug; D020847:Estrogen Receptor Modulators / Q000633:toxicity*; D005260:Female; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D020847:Estrogen Receptor Modulators; D018976:Insulin-Like Growth Factor Binding Protein 6; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II