Growth stimulation of a rat pituitary cell line MtT/E-2 by environmental estrogens in vitro and in vivo.
Endocrine disruptors are a diverse group of chemicals that alter the functions of the endocrine system. A large proportion of endocrine disruptors have estrogenic effects, thus are called environmental estrogens. In the present study, an estrogen (E2) responsive rat pituitary cell line, MtT/E-2, was employed to examine 1) the potency of several endocrine disruptors including bisphenol A (BPA), o,p'-DDD, methoxychlor, 1,2,3,4,5,6-hexachlorocyclohexane (HCH) and dibromoacetic acid (DBAA) in terms of E2 responsive pituitary cell growth; 2) whether BPA has estrogenic action in vivo causing the growth of MtT/E-2 cells grafted in rats. Binding assays showed the test chemicals were able to compete with 3H-E2 binding to the estrogen receptor (ER). The compounds also stimulated growth of MtT/E-2 cells at rates corresponding to their ER binding affinity. Their transcription activation of an (ERE)3-SV40-luciferase reporter in MtT/E-2 cells was comparable to their stimulation of cell growth, with the exception of HCH which showed little induction of cell growth but strong stimulation in ERE dependent transcription activation. MtT/E-2 cells were inoculated into ovariectomized female F344 rats treated with E2 or BPA. The first tumors were noted at day 22 in the E2 treated group, at day 25 in the highest dose of BPA group and at day 41 in the control group. These results suggest 1) that the growth assay with MtT/E-2 cells provides simple and sensitive test for detection of estrogenic activity of environmental chemicals; 2) that BPA has estrogenic potency to stimulate E2 responsive cell growth in vivo as well as in vitro.
Maruyama
S
S
Department of Cancer Research, Research Institute for Radiation Biology and Medicine, Hiroshima University, Japan.
Fujimoto
N
N
Yin
H
H
Ito
A
A
D000085:Acetates / Q000494:pharmacology; D000818:Animals; D001559:Benzhydryl Compounds; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D001556:Hexachlorocyclohexane / Q000494:pharmacology; D008156:Luciferases / Q000378:metabolism; D008731:Methoxychlor / Q000494:pharmacology; D008939:Mitotane / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D014599:Uterus / Q000187:drug effects; D000098826:Bisphenol A Compounds
D000085:Acetates; D001559:Benzhydryl Compounds; D004958:Estradiol; D004967:Estrogens; D001556:Hexachlorocyclohexane; D008156:Luciferases; D008731:Methoxychlor; D008939:Mitotane; D010636:Phenols; C088674:dibromoacetic acid; C006780:bisphenol A; D000098826:Bisphenol A Compounds