Parathyroid hormone (PTH), which is elevated in patients with chronic renal failure, has been shown to participate in the development of vascular calcification. Previous studies have demonstrated that PTH may promote endothelial expressions of proinflammatory parameters. On the basis of these data, we evaluated whether PTH may have an impact on endothelial osteoprotegerin (OPG), a vascular protective factor which may control vascular calcification. Endothelial cells were stimulated with 10^-12-10^-10 mol/L PTH. Protein kinase C (PKC) and protein kinase A (PKA) are the main cellular pathways of PTH. Inhibitors and activators of PKC or PKA were used to determine if these signaling pathways are involved in the control of endothelial OPG. PTH induced a decrease in OPG secretion and mRNA expression. Treatment of PTH-stimulated cells by Calphostin C (PKC inhibitor) induced a further decrease in OPG secretion, while Rp-cAMP (PKA inhibitor) had no additional effect. In non-stimulated cells, PKC activator significantly stimulated OPG secretion, while PKA activator was associated with a decline. These effects were blunted in the presence of Calphostin C and Rp-cAMP respectively. An increase in OPG secretion induced by a PKC activator indicates that the basal OPG secretion is mediated through PKC. The decrease induced by a PKA activator, which is similar to that observed with PTH, suggests that, the action of PTH on OPG secretion and mRNA expression may be due to the PKA pathway.