High extracellular calcium increases the production of a parathyroid hormone-like activity by cultured leydig tumor cells associated with humoral hypercalcemia

Abstract

Cultured Leydig tumor cells produce a parathyroid hormone (PTH)-like activity, but little is known about the regulation of the release of this factor. In the present work, we investigated the influence of the extracellular calcium concentration on the production of adenylate cyclase-stimulating activity, as evaluated in the osteoblast-like PTH-responsive cell line UMR 106. Medium conditioned in the presence of 0.4 mM or 3 mM Ca elicited a 5.8 +/- 0.4-fold and 10.3 +/- 0.9-fold increase over basal of cAMP production, respectively (p less than 0.001, n = 11 experiments). This effect, which was selective for PTH-like activity, was detectable after 2 h of incubation and maximal at 6-14 h. It was abolished by the protein synthesis inhibitor cycloheximide, but not by actinomycin D or cordycepin, suggesting a post-transcriptional site of action. Thus, the production of a tumoral circulating factor implicated in the pathogenesis of humoral malignant hypercalcemia may be influenced in a positive way by an increase in extracellular calcium concentration.