Stimulation of parathyroid hormone secretion by phorbol esters is associated with a decrease of cytosolic calcium

Abstract

Unlike in other endocrine systems calcium inhibits parathyroid hormone (PTH) secretion and this inhibition is paralleled by a rise of cytosolic calcium concentration ([Ca] i). Because of evidence that diglyceride levels and protein kinase C activity are also decreased by high extracellular calcium we have investigated the effects of 12- O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C, on [Ca] i and PTH secretion using dispersed bovine parathyroid cells. At 1.5 mM medium calcium TPA enhanced PTH secretion and caused reduction of [Ca] i from 639 ± 36 nM (SE) to 335 ± 21 nM ( P < 0.001); at 0.5 mM calcium TPA was ineffective. Moreover, TPA suppressed the rise of [Ca] i evoked by high extracellular calcium. Thus TPA presumably stimulates PTH secretion via activation of protein kinase C, and the lowering of [Ca] i may be a secondary event related to diglyceride availability.