Regulation of parathyroid hormone release by protein kinase-C is dependent on extracellular calcium in bovine parathyroid cells

Bart L. Clarke, Christian Hassager, Lorraine A. Fitzpatrick

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The purpose of this study was to evaluate regulation of PTH secretion by protein kinase-C (PKC) in adult bovine parathyroid cells. Extracellular calcium (Ca2+e) is the main physiological regulator of PTH secretion. Putative second messengers include intracellular calcium (Ca2+i), cAMP, inositol trisphosphate, and diacylglycerol (DAG). Both DAG and Ca2+i activate PKC. Certain phorbol esters mimic the effect of DAG and cause prolonged stimulation of PKC. The stimulatory phorbol esters 12-0-tetradecanoylphorbol acetate (1 µM) and phorbol-12, 13-dibutyrate (1 µM) did not affect PTH secretion at low Ca2+e, but increased both individual cell secretion and recruitment of cells to secrete at high Ca2+e. The PKC inhibitors H7 (1 µM), tamoxifen (10 µm), and sphinganine (5 µm) inhibited PTH release at low Ca2+e(0.1 and 0.2 mM) and decreased cell recruitment over the physiological range of Ca2+e- The nonstimulatory phorbol esters 4α-phorbol-12, 13-didecanoate (1 µM) and phorbol-13-monoacetate (1 µM) had no effect on PTH secretion. To assess the mechanism by which certain phorbol esters stimulated PTH secretion, in situ hybridization for PTH mRNA was performed. Phorbol-12, 13-dibutyrate (1 µM) qualitatively increased steady state PTH mRNA levels compared to control values. We conclude that 1) PKC stimulation increased PTH secretion at high Ca2+e, but not at low Ca2+e; 2) PKC inhibition decreased PTH secretion at low Ca2+e; and 3) PKC stimulation increased steady state PTH mRNA levels. These data suggest that PKC plays an important regulatory role in the synthesis and secretion of PTH.

Original languageEnglish (US)
Pages (from-to)1168-1175
Number of pages8
JournalEndocrinology
Volume132
Issue number3
DOIs
StatePublished - Mar 1993

ASJC Scopus subject areas

  • Endocrinology

Fingerprint Dive into the research topics of 'Regulation of parathyroid hormone release by protein kinase-C is dependent on extracellular calcium in bovine parathyroid cells'. Together they form a unique fingerprint.

Cite this