THE UNLIGANDED ESTROGEN-RECEPTOR (ER) TRANSDUCES GROWTH-FACTOR SIGNALS

In the absence of serum and estrogen, we show that the growth of the p rolactin secreting pituitary tumour cell line, GH, is stimulated by in sulin and insulin-like growth factor-1 (IGF-1) and this response is bl ocked by the steroidal antiestrogens, ICI 164384 and ICI 182780. From conditioned medium (CM) experiments, growth of low density cells (10k/ cm(2)) is increased by the addition of CM from high density cells (100 k/cm(2)) and this growth effect is also blocked by antiestrogen. Trans fection studies with a Delta MTV-ERE-LUC reporter plasmid show that in the absence of estrogen and serum, both insulin and IGF-1 induce luci ferase expression and this is blocked by the pure antiestrogens. No ef fect of these treatments was apparent when parallel experiments were c onducted with a plasmid construct lacking the vitellogenin estrogen re sponse element. From these and other data discussed in this report, we conclude that for GH, cells, in the absence of estrogen and serum, th e ER is transcriptionally activated by intracellular peptide factor pa thways and by this means, acts as the key nuclear factor inducing mito genesis in response to autocrine and exogenously added growth factors.