A rat pituitary tumor sub-line MtT/E-2 was established from a rat pituitary tumor cell line MtT/E. Its growth was found to depend on the presence of estradiol (E2) in culture media at 10(-13)-10(-9) M, whereas the original cell line MtT/E proliferated autonomously. The recently discovered PTTG (pituitary tumor transforming gene) is highly expressed in this cell line, although not regulated by E2. On the other hand, E2 induced c-myc and cyclin D1 proteins in MtT/E-2, which contains a lot (220+/-18 fmol/mg protein) of estrogen receptor demonstrated by RT-PCR analysis to be predominantly alpha type. MtT/E-2 secretes growth hormone which is, interestingly, regulated by retinoic acid and dexamethasone rather than thyroid hormones.