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 MESSENGER-RNA

The principal regulator of parathyroid hormone (PTH) secretion is ioni zed calcium, but other factors are also known to modulate PTH secretio n, such as vitamin D, estrogen, and recently inorganic phosphate. Inte rleukin-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 fac tor in the control of PTH secretion. We investigated the effect in vit ro of IL-1 beta on PTH release, PTHmRNA and the mRNA for the extracell ular calcium-sensing receptor (CaR) levels in preparations of bovine p arathyroid cells. PTH secretion from cultured parathyroid tissue slice s was significantly inhibited in a medium containing IL-1 beta at a co ncentration 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 ill prepara tions 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. CaRmRN A levels to 180% of control, whereas no change in PTHmRNA was found. I L-1ra abolished the upregulating effect of IL-1 beta on the CaRmRNA. T his study demonstrates a direct effect in vitro of IL-1 beta on PTH se cretion from bovine parathyroid glands, an effect which may be mediate d at least in part through the specific IL-1 receptor causing an upreg ulation of the calcium-sensing receptor mRNA. IL-1 might therefore pla y a role as a auto- and/or paracrine factor in the regulation of the P TH secretion. (C) 1997 Academic Press.