GH4CI cells are a clonal strain of rat pituitary cells that synthesize and secrete prolactin and growth hormone . Chronic treatment (longer than 24 h) of GH4CI cells with epidermal growth factor (EGF) (10 -8 M) decreased by 30-40% both the rate of cell proliferation and the plateau density reached by cultures . Inhibition of cell proliferation was accompanied by a change in cellular morphology from a spherical appearance to an elongated flattened shape and by a 40-60% increase in cell volume . These actions of EGF were qualitatively similar to those of the hypothalamic tripeptide thyrotropin-releasing hormone (TRH) (10 -' M) which decreased the rate of cell proliferation by 10-20% and caused a 15% increase in cell volume. The presence of supramaximal concentrations of both EGF (10-A M) and TRH (10-' M) resulted in greater effects on cell volume and cell multiplication than either peptide alone . EGF also altered hormone production by GH4CI cells in the same manner as TRH . Treatment of cultures with 10 -A M EGF for 2-6 d increased prolactin synthesis five-to ninefold compared to a two-to threefold stimulation by 10 -' M TRH . Growth hormone production by the same cultures was inhibited 40% by EGF and 15% by TRH . The half-maximal effect of EGF to increase prolactin synthesis, decrease growth hormone production, and inhibit cell proliferation occurred at a concentration of 5 x 10 -" M . Insulin and multiplication stimulating activity, two other growth factors tested, did not alter cell proliferation, cell morphology, or hormone production by GH 4C 1 cells, indicating the specificity of the EGF effect . Fibroblast growth factor, however, had effects similar to those of EGF and TRH . Of five pituitary cell strains tested, all but one responded to chronic EGF treatment with specifically altered hormone production . Acute treatment (30 min) of GH4CI cells with 10 -' M EGF caused a 30% enhancement of prolactin release compared to a greater than twofold increase caused by 10 -' M TRH . Therefore, although EGF and TRH have qualitatively similar effects on 786 J . CELL BIOLOGY
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