Regulation of parathyroid hormone messenger RNA levels by protein kinase A and C in bovine parathyroid cells

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Abstract
Secretion of parathyroid hormone (PTH) is regulated by Ca2+ as well as by protein kinases A and C. In this study we report that protein kinases A and C regulate PTH messenger RNA levels in vitro in dispersed bovine parathyroid cells. Incubation of bovine parathyroid cells with cholera toxin (10−9 M), which activates adenylate cyclase and indirectly stimulates protein kinase A, increased PTH mRNA levels about 2-fold after 3 and 7 h incubation, but not at 24 h. Incubation with pertussis toxin (5 × 10−9 M), which blocks the high-calcium-mediated inhibition of cyclic adenosine monophosphate accumulation in these cells, also reversed the inhibition of PTH mRNA levels at high Ca2+ (2.0 mM) with a marked increase in PTH mRNA levels. Pertussis toxin also increased PTH mRNA at a low extracellular Ca2+ concentration (0.7 mM) (4-fold increase) and a normal concentration (1.25 mM) (2-fold increase). Inhibition of protein kinase C both by staurosporine (1 × 10−8 M) and by prolonged incubation with the phorbol ester phorbol 12-myristate 13-acetate (PMA) (1 × 10−7 M), decreased PTH mRNA levels at 24 h, reaching approximately 40% and 5% of control, respectively. Staurosporine and PMA had no effect on PTH mRNA levels at 3 h. The inactive phorbol ester, phorbol 12–13-diburyrate (PDBu), had no effect on PTH mRNA levels at 1 and 24 h. There were no changes in a control gene 18S RNA in these studies. PMA at 24 h, which may down-regulate protein kinase C activity, decreased PTH mRNA levels, suggesting that protein kinase C is necessary for normal PTH gene expression. These results suggest that both protein kinase A and C are involved in the regulation of PTH gene expression.
Funding Information
  • Thyssen Foundation