Growth stimulation of a rat pituitary cell line MtT/E-2 by environmental estrogens in vitro and in vivo

Endocrine disrupters are a diverse group of chemicals that alter the functions of the endocrine system. A large proportion of endocrine disrupters have estrogenic effects, thus are called environmental estrogens. In the present study, an estrogen (E-2) responsive rat pituitary cell line, MtT/E-2, was employed to examine 1) the potency of several endocrine disrupters including bisphenol A (BPA), o,p'-DDD, methoxychlor, 1,2,3,4,5,6-hexachlorocyclohexane (HCH) and dibromoacetic acid (DBAA) in terms of E-2 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 H-3-E-2 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 E-2 or BPA. The first tumors were noted at day 22 in the E-2 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 E-2 responsive cell growth in vivo as well as in vitro.