Acute parathyroid hormone secretory dynamics: hormone secretion from normal primate and adenomatous human tissue in response to changes in extracellular calcium concentration.

Abstract

PTH secretion has been evaluated extensively using short term incubation techniques, but these methods cannot be used to adequately evaluate the early phases of PTH secretion. We developed a dispersed cell perifusion system to study these acute secretory events. Responses to low calcium conditions were studied using dispersed cells from normal primate and adenomatous human parathyroid tissue. When these cell were perifused with 1.0 mM calcium medium, PTH secretion was stable, but increased within minutes in a dose-dependent manner in response to a lowering of extracellular calcium concentrations. Similarly, PTH secretion quickly declined when cells were exposed to higher extracellular calcium concentrations. In studies of cells from 11 human adenomas, the mean maximum secretion in response to 0.25 mM calcium conditions was 587 +/- 330% (+/- SD) of that in response to 1.0 mM calcium. The magnitude of the response to low calcium stimulation was variable, and cells from two additional adenomas failed to respond to low calcium stimulation despite responses to other secretogogues. Variation in the rate of increase in stimulated PTH secretion was also found among the adenomas examined (128 +/- 95% of baseline/min), and the rate of increase in PTH release and the eventual maximum rate of release were positively correlated. In studies of cells from 4 normal primates (rhesus macaque), the maximum response to 0.25 mM Ca2+ (544 +/- 118% of baseline) and the rate of increase in PTH secretion (95 +/- 35% of baseline/min) were similar to those in adenomatous human tissue. These results indicate that 1) acute PTH secretion can be studied in vitro, and that it appears to be similar to the in vivo process; 2) there is a wide variation among adenomatous tissues in the magnitude of secretion stimulated by low calcium concentrations; 3) in addition to varied magnitude of secretion, the rate at which hormone secretion increases in response to a low calcium stimulus varied among adenomas; and 4) PTH secretion from human adenomatous tissue is similar to that from normal primate tissue in both the rate and magnitude of response.