Manipulation of calciumhomeostatic mechanisms in man: what are the possibilities?
The aim of our studies on parathyroid hormone dynamics were to establish standardized methods for induction of hypocalcaemia, sequential hypercalcaemia and normocalcaemia and sequential hypocalcaemia and hypercalcaemia suitable for careful and detailed evaluation of the PTH(1-84) secretion in vivo. We found that at least two distinctly different mechanisms of PTH(1-84) secretion serve to protect normal humans against hypo- and hypercalcaemia. First, an initial decrement of B-Ca2+ leads to a large transient release of preformed PTH(1-84) from the cellular depots, whereas, an initial increment of B-Ca2+ leads to almost immediate suppression of PTH(1-84) release. The change in PTH(1-84) release is rate dependent in either direction and demonstrable even at small decrements or increments of B-Ca2+. This mechanism of delta regulation provide a strong homeostatic mechanism for maintaining a stable extracellular calcium level during slow as well as rapid changes in B-Ca2+. Second, a mechanism of steady state regulation for continued secretion takes over, being dependent on the absolute B-Ca2+ concentration, which probably controls the synthesis of PTH(1-84) molecules. Selective investigation of the steady state response to hypocalcaemia demands elimination of preformed PTH(1-84). With this precaution, we described the inverse sigmoidal relationship in vivo between the steady state pairs of B-Ca2+ and S-PTH(1-84) in normal humans. The calcium set-points of Brown measured by this computer method were significantly lower than Parfitt's calcium set-points in normal humans, but strikingly well correlated. This observation supporting the view that Brown and Parfitt describe two different points on the same sigmoidal curve, corresponding to 50% and about 85% inhibition of PTH(1-84) in normal humans.
Schwarz
Peter
P
Osteoporosis and Metabolic Bone Unit, Dept. of Clinical Biochemistry, Copenhagen University Hospitals, H:S Hvidovre Hospital, DK-2650 Hvidovre. peter.schwarz@hh.hosp.dk
D002122:Calcium Chloride / Q000097:blood / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D006934:Hypercalcemia / Q000097:blood*; D006996:Hypocalcemia / Q000097:blood*; D010281:Parathyroid Hormone / Q000097:blood*
D010281:Parathyroid Hormone; D002122:Calcium Chloride