REGULATION OF PARATHYROID-HORMONE GENE-EXPRESSION AND PEPTIDE SECRETION IN HUMAN PARATHYROID CELLS

In cell cultures prepared from human parathyroid adenomas, parathyroid hormone (PTH) mRNA expression decreased slowly. During short-term inc ubations (less than 24 h), a low calcium concentration (0.5 mmol/l) an d protein kinase C activator TPA (12-O-tetradecanoyl phorbol 13-acetat e) (160 nmol/l) increased PTH secretion (60%; p<0.05), while a high ex tracellular calcium concentration (2.5 mmol/l) reduced PTH secretion ( 60%; p<0.05). The TPA could block the inhibitory effect of a high calc ium level on PTH peptide secretion. All these agents had no effect on PTH mRNA accumulation in short-term experiments. In long-term cultures (more than 24 h), a low calcium level increased and a high calcium le vel reduced both PTH mRNA (85 and 34%; p<0.05) and peptide secretion ( 140 and 80%; p<0.05), respectively. The TPA reduced PTH mRNA accumulat ion down to 30% (p<0.05) and PTH secretion down to 14% (p<0.05) in a t ime- and dose-dependent fashion. The TPA also reversed the stimulatory effect of hypocalcemia on PTH mRNA accumulation and peptide secretion . Protein kinase C inhibitors staurosporine (100 nmol/l) and H-7 (1-(5 -isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride) (50 mu mol/ l) had similar effects to TPA on PTH gene expression and peptide secre tion in long-term cultures. The results support the hypothesis that ex tracellular calcium regulates PTH mRNA accumulation and PTH secretion via protein kinase C.