Inhibition of PTH secretion by interleukin-1 beta in bovine parathyroid glands in vitro is associated with an up-regulation of the calcium-sensing receptor mRNA.

ABSTRACT

The principal regulator of parathyroid hormone (PTH) secretion is ionized calcium, but other factors are also known to modulate PTH secretion, such as vitamin D, estrogen, and recently inorganic phosphate. Interleukin-1 (IL-1) possesses a wide variety of biological activities and is produced by leukocytes as well as by various other cells including cells from endocrine tissues and might play a role as a paracrine factor in the control of PTH secretion. We investigated the effect in vitro of IL-1 beta on PTH release, PTHmRNA and the mRNA for the extracellular calcium-sensing receptor (CaR) levels in preparations of bovine parathyroid cells. PTH secretion from cultured parathyroid tissue slices was significantly inhibited in a medium containing IL-1 beta at a concentration of 2000 pg/ml (PTH in % of control 63.5 +/- 5.3), n=10 (p<0.01). The inhibitory effect of IL-1 beta was not found in preparations of dispersed cells. The inhibitory effect of IL-1 beta could be counteracted by the IL-1 receptor antagonist (IL-1ra), indicating that the inhibitory effect was mediated through the specific IL-1 receptor on the parathyroid cells. IL-1 beta (2000 pg/ml) up-regulated CaRmRNA levels to 180% of control, whereas no change in PTHmRNA was found. IL-1ra abolished the upregulating effect of IL-1 beta on the CaRmRNA. This study demonstrates a direct effect in vitro of IL-1 beta on PTH secretion from bovine parathyroid glands, an effect which may be mediated at least in part through the specific IL-1 receptor causing an upregulation of the calcium-sensing receptor mRNA. IL-1 might therefore play a role as a auto- and/or paracrine factor in the regulation of the PTH secretion.