Dexamethasone and calcium interact in the regulation of parathormone and chromogranin-A secretion and messenger ribonucleic acid levels in parathyroid cells

Abstract

We investigated the interaction of dexamethasone and Ca2+ on the secretion of PTH and chromogranin-A (CgA) by porcine parathyroid cells in culture and on the cellular levels of PTH and CgA mRNA. Freshly dispersed parathyroid cells were cultured for 6 days in Ham's F-12 medium containing 10% fetal calf serum and 1 mM Ca2+. The experiments were initiated at 0.5 or 3.0 mM Ca2+ in 0.5% serum with or without dexamethasone for an additional 24 or 48 h. Secretion of PTH and CgA was 50-60% less, and the respective mRNAs levels were about 75% lower at 3.0 than at 0.5 mM Ca2+. Dexamethasone (10(-9)-10(-7) M) stimulated the secretion of PTH in a dose-dependent fashion about 2-fold at both 3.0 and 0.5 mM Ca2+ and increased the PTH mRNA level 15-fold at the high and 3-fold at the low Ca2+ concentration. In contrast, the direction of action of dexamethasone on the secretion of CgA and CgA mRNA was dependent upon the Ca2+ concentration. At 3.0 mM Ca2+, dexamethasone increased CgA secretion and mRNA levels about 2- and 8-fold, respectively. In contrast, at 0.5 mM Ca2+ dexamethasone decreased CgA secretion to one half and its mRNA to one tenth that cells without the glucocorticoid. The stimulatory action of dexamethasone on PTH and CgA mRNA could be noted in 12 h or less and continued through 24-48 h. These results demonstrate a decoupling of PTH and CgA secretion and gene regulation. Our data accord with a role for CgA as an autocrine regulator of parathyroid gland secretion.