GLUCOCORTICOIDS DECREASE THE PRODUCTION OF PARATHYROID HORMONE-RELATED PROTEIN IN-VITRO BUT NOT IN-VIVO IN THE WALKER-CARCINOSARCOMA-256 RAT MODEL

50-90% of cases, humoral hypercalcemia of malignancy (HHM) is due to t umor secretion of parathyroid hormone-related protein (PTHrP), Glucoco rticoids are sometimes used as calcium lowering agents and there are i n vitro results showing that glucocorticoids diminish PTHrP production , In this study we tested whether the serum-calcium-lowering effect of glucocorticoids is due to decreased PTHrP production by the tumor, As an animal and cell culture model we used the Walker carcinosarcoma (W CS) 256, a rat mammary carcinoma cell line producing PTHrP, In vitro, dexamethasone caused a dose-dependent inhibition of PTHrP production, whereby already 1-5 nmol/L revealed a significant decrease by WCS 256 cells, In contrast to these in vitro results, in WCS 256 tumor-bearing rats, dexamethasone (4 mg/kg body weight on day 4, and 1 mg/kg body w eight from day 5 until day 7 after WCS transplantation; circulating de xamethasone levels >20 nmol/L) did not decrease PTHrP production, PTHr P secretion, serum calcium, or tumor weight in vivo, We conclude that, in this PTHrP-mediated model of humoral hypercalcemia of malignancy, glucocorticoids do not decrease PTHrP production and secretion in vivo and do not show a calcium-lowering effect.