The effect of 1,25-dihydroxyvitamin D 3 on human osteoblast-like osteosarcoma cell: Modification of response to PTH

Abstract

The influence of 1,25-dihydroxyvitamin D 3 [1,25 (OH) 2D 3] on adenylate cyclase responsiveness in cultured osteoblastic cells was studied using a human osteosarcoma cell line SaOS-2. 1,25(OH) 2D 3 treatment had no effect on cell growth, cell protein and alkaline phosphatase activity. 1,25(OH) 2D 3 did not alter the basal production of cyclic AMP (cAMP) in intact cells, but the cAMP formation in response to parathyroid hormone (PTH), isoproterenol (ISO) and cholera toxin was attenuated by 1,25(OH) 2D 3. The response to forskolin, however, was unaffected by 1,25(OH) 2D 3 treatment. Islet activating protein failed to modify these 1,25(OH) 2D 3 effect. In cell free experiments, 1,25(OH) 2D 3 showed similar effect — that is, PTH and ISO-stimulated adenylate cyclase activity were attenuated, but forskolin-stimulated adenylate cyclase was unaffected. 1,25(OH) 2D 3 treatment had no effect on the kinetics of PTH binding to PTH receptor and on the ADP ribosylation of GTP stimulatory binding protein (G s) in SaOS-2 cells. According to these results, 1,25(OH) 2D 3 appeared to change the coupling of G s with adenylate cyclase, but dose not affect receptor, G s and adenylate cyclase themselves, nor GTP inhibitory binding protein.