Induction of distinct phenotypes in clonal and variant GH4 pituitary cells

Summary GH cells are a widely used cell strain for the investigation of mechanisms regulating hormone release and synthesis. This report identifies two inducible phenotypes of the GH₄ clone (epithelioid and motile) which may extend studies of this well-characterized cell line to different stages of pituitary cell development. GH₄C₁ cells treated in suspension with epidermal growth factor plus tetradecanoylphorbol acetate aggregate to form large epithelioid colonies with extensive cell-to-cell and cell-to-substratum adhesion. These cells cease replicating within 48 h, increase 50% in cell volume, and synthesize 40-fold more prolactin. A GH₄C₁ variant with enhanced substratum adhesion and little or no cell-to-cell adhesion (GH₄S₁), responds differently to this treatment. These cells cease replicating immediately, show increased cell separation, develop leading lamellae, and display locomotory activity. Each phenotype coexists in mixed cultures of GH₄C₁ and GH₄S₁ cells. This indicates that the different inducible response of the variant does not result from autocrine secretion. A molecular basis for cell-to-cell adhesion in GH₄ cells was investigated. GH₄C₁, but not the variant cells, express a 180 kDa immunoreactive protein indistinguishable from an isoform of the neural cell adhesion molecule. Therefore the absence of cell-to-cell adhesion and inability to develop extensive cell-to-cell adhesion characteristic of the epithelioid phenotype may result from altered expression of the neural cell adhesion molecule. These findings are important because they have defined an in vitro approach to investigate genetic and cellular changes associated with the development and progression of pituitary cell phenotype. This study was initiated in the laboratory of Dr. A. H. Tashjian, Jr., under the support of grant DK11011 from the National Institutes of Health, Bethesda, MD. The completion of this study was supported by the Medical University of South Carolina Biomedical Support Grant of 1987–1988 and the American Cancer Society grant 1N-175.