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 gp140trk and the gp75 components of the nerve growth factor (NGF) receptor and that NGF dictates a nonneuronal type of differentiation of this cell line of ectodermal 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 following days of exposure, was paralleled by a change in the hormone production. The secretion of PRL was increased 6-fold, but that of GH was remarkably inhibited. Moreover, GH-3 cells expressed the mammotroph-specific D-2 receptor protein in response to NGF, as shown by binding with the D-2 receptor ligand N-(p-aminophenetyl)spiperone coupled to fluorescein. The present data thus show that NGF induces the differentiation of GH-3 cells into one of their physiological counterparts, the mammotroph cell, and together with the finding that NGF receptors are expressed in the anterior pituitary suggest a physiological role for the neurotrophic factor in pituitary ontogenesis.
Department of Biomedical Sciences and Biotechnology, University of Brescia School of Medicine, Italy.
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Missale
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Boroni
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Sigala
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Zanellato
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Dal Toso
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Balsari
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Spano
D002454:Cell Differentiation / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D013006:Growth Hormone / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism; D010641:Phenotype; D010903:Pituitary Gland, Anterior / Q000166:cytology* / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D014407:Tumor Cells, Cultured
D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D011388:Prolactin; D013006:Growth Hormone; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA