Parathyroid Hormone Related Peptide (1-34) and 1,25-Dihydroxyvitamin D, Have No Additive Effects on Bone Tartrate Resistant Acid Phosphatase Activity in Fetal Rat Calvaria Cultures

Parathyroid hormone related peptide (PTHrP) and 1,25-dihydroxyvitamin D are known to be resorptive agents which could contribute to the development of hypercalcemia in humoral hypercalcemia of malignancy (HHM) syndrome in Walker 256 tumor bearing rats. In order to clarify some aspects about the relative contribution of these factors to bone resorption, we have determined the effects produced by PTHrP (1-34) and/or 1,25(OH)2D3 on tartrate resistant acid phosphatase (TRAP), a biochemical marker of bone resorption, in fetal rat calvaria cultures. At the same time, bovine parathyroid hormone (PTH) (1-34) was used as a control in the experiments in order to compare its effects with those produced by the other two agonists. In the present work, 10(-7) M PTH (1-34), 10(-7) M PTHrP (1-34) and 10(-8) M or 10(-10) M 1,25(OH)2D3 produced a significant increase in TRAP activity, when these agonists were added to the calvaria culture. Surprisingly, and in spite of the different ways of action of PTH, PTHrP and 1,25(OH)2D3, their actions are not additive in our experiment. The results of the present work suggest that any of the two implicated factors PTHrP or 1,25(OH)2D3 could be individually responsible for the high rate of bone resorption that takes place in HHM syndrome in Walker 256 carcinosarcoma bearing rats, although other different agents, like TGF, could also be implicated.