INVOLVEMENT OF THE ESTROGEN-RECEPTOR IN THE GROWTH-RESPONSE OF PITUITARY-TUMOR CELLS TO INTERLEUKIN-2

Having recently demonstrated in separate studies that the T-cell cytok ine, interleukin-2, induces the growth of the pituitary tumor cell lin e GH(3) and that in the same cells, the estrogen receptor mediates the mitogenic effect of growth factors, we sought here to determine wheth er the estrogen receptor was involved in the response to interleukin-2 . We demonstrate that under steroid and serum free growth conditions, the pure antiestrogen, ZM 182780, blocks the mitogenic response of GH( 3) cells to interleukin-2. Transfection studies with a reporter plasmi d responsive to the transcriptionally active estrogen receptor show th at even in the absence of ligand, the estrogen receptor in these cells is transcriptionally active and this can be increased by interleukin- 2. Further studies on the two estrogen receptor regulated proteins, th e progesterone receptor and prolactin, showing that the levels of thes e proteins were increased by exposure of cells to interleukin-2, suppo rt the idea of a cross-talk between the estrogen receptor and interleu kin-2 signal transduction. (C) 1994 Academic Press, Inc.