Abstract
Ras homolog enriched in striatum (Rhes) is a member of the Ras family of small GT-Pases detected in the thyroid. Rhes inhibits signal transduction from Gas protein. In this study we investigated whether Rhes can interfere with stimulation of cAMP/protein kinase A (PKA) pathway of TSH, FSH and LH receptors (TSHr, FSHr, LHr) and of activated TSHr mutants. Receptors were transiently transfected in COS-7 cells with or without Rhes; cAMP was evaluated in basal conditions and after hormone stimulation. Constitutive and bovine TSH (bTSH)-stimulated activity of wild type (wt) and mutated TSHr was inhibited after Rhes co-transfection. Rhes decreased cAMP after FSH and hCG β-subunit (βhCG) stimulation in cells expressing the cognate receptors. In binding experiments Rhes, as another membrane protein, sodium/iodide symporter (NIS), reduced membrane expression of wt TSHr (wtTSHr). In conclusion, Rhes can interfere with the functional activity of wt and mutated TSHr and with the respective hormone-stimulated cAMP production of FSHr and LHr. This interference is not specific and due to the co-expression of two membrane proteins.
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Agretti, P., De Marco, G., Pinchera, A. et al. Ras homolog enriched in striatum inhibits the functional activity of wild type thyrotropin, follicle-stimulating hormone, luteinizing hormone receptors and activating thyrotropin receptor mutations by altering their expression in COS-7 cells. J Endocrinol Invest 30, 279–284 (2007). https://doi.org/10.1007/BF03346294
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DOI: https://doi.org/10.1007/BF03346294