NERVE GROWTH-FACTOR DIRECTS DIFFERENTIATION OF THE BIPOTENTIAL CELL-LINE GH-3 INTO THE MAMMOTROPH PHENOTYPE

GH-3 is an established cell line which, for the production of both PRL and GH, may be related to the bipotential somatomammotroph from which both somatotroph and mammotroph cells derive. In the present study we first report that GH-3 cells express both the gpl40trk and the gp75 c omponents of the nerve growth factor (NGF) receptor and that NGF dicta tes a nonneuronal type of differentiation of this cell line of ectoder mal origin. After exposure to NGF, GH-3 cells markedly decreased their proliferation rate. This effect, which was maximal (50% inhibition) 3 days after beginning the treatment and was maintained during the foll owing days of exposure, was paralleled by a change in the hormone prod uction. The secretion of PRL was increased 6-fold, but that of GH was remarkably inhibited. Moreover, GH-3 cells expressed the mammotroph-sp ecific D-2 receptor protein in response to NGF, as shown by binding wi th the D-2 receptor ligand N-(p-aminophenetyl)spiperone coupled to flu orescein. The present data thus show that NGF induces the differentiat ion of GH-3 cells into one of their physiological counterparts, the ma mmotroph cell, and together with the finding that NGF receptors are ex pressed in the anterior pituitary suggest a physiological role for the neurotrophic factor in pituitary ontogenesis.