Epidermal growth factor and thyrotropinreleasing hormone act similarly on a clonal pituitary cell strain: Modulation of hormone production and inhibition of cell proliferation

Abstract

GH4C1 cells are a clonal strain of rat pituitary cells that synthesize and secrete prolactin and growth hormone. Chronic treatment (longer than 24 h) of GH4C1 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) (10-7 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 (10-8 M) and TRH (10-7 M) resulted in greater effects on cell volume and cell multiplication than either peptide alone. EGF also altered hormone production by GH4C1 cells in the same manner as TRH. Treatment of cultures with 10-8 M EGF for 2-6 d increased prolactin synthesis five- to ninefold compared to a two- to threefold stimulation by 10-7 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 × 10-11 M. Insulin and multiplication stimulating activity, two other growth factors tested, did not alter cell proliferation, cell morphology, or hormone production by GH4C1 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 GH4C1 cells with 10-8 M EGF caused a 30% enhancement of prolactin release compared to a greater than twofold increase caused by 10-7 M TRH. Therefore, although EGF and TRH have qualitatively similar effects on GH4C1 cells, their powers to affect hormone release acutely or hormone synthesis and cell proliferation chronically are distinct. © 1980, Rockefeller University Press., All rights reserved.