Cell-specificity of transforming growth factor-beta response is dictated by receptor bioavailability.

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Cell-specificity of transforming growth factor-beta response is dictated by receptor bioavailability.

J Mol Endocrinol. 2006 Jun;36(3):591-600

Authors: Suszko MI, Woodruff TK

Abstract

Members of the transforming growth factor-beta (TGFbeta) family control diverse cellular responses including differentiation, proliferation, controlled cell death and migration. The response of a cell to an individual ligand is highly restricted yet the signaling pathways for TGFbeta, activin and bone morphogenic proteins share a limited number of receptors and activate similar intracellular cytoplasmic co-regulators, Smads. A central question in the study of this family of ligands is how cells titrate and integrate each TGFbeta-like signal in order to respond in a cell- and ligand-specific manner. This study uses the pituitary gonadotrope cell line, LbetaT2, as a model to delineate the relative contribution of TGFbeta and activin ligands to follicle-stimulating hormone (FSH) biosynthesis. It was found that pituitary gonadotrope cells do not express the TGFbeta type II (TbetaRII) receptor and are therefore not responsive to the TGFbeta ligand. Transfection of the receptor restores TGFbeta signaling capabilities and the TGFbeta-mediated stimulation of FSHbeta gene transcription in LbetaT2 cells. Consequently, we evaluated the presence of the TbetaRII in the adult mouse pituitary. TbetaRII does not co-localize with FSH-producing cells; however it is detected on the cell surface of prolactin- and growth hormone-positive cells. Taken together, these results suggest that the bioavailability of the TGFbeta-specific receptor rather than TGFbeta dictates pituitary gonadotrope selectivity to activin, which is necessary to maintain normal reproductive function. It is likely that the ligand-restricted mechanisms employed by the gonadotrope are present in other cells, which could explain the distinct control of many cellular processes by members of the TGFbeta superfamily.
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PMID: 16720726 [PubMed - indexed for MEDLINE]