Due to the importance of Ca2+ in the regulation of vital cellular and
tissue functions, the concentration of Ca2+ in body fluids is closely
guarded by an efficient feedback control system. This system includes
Ca2+-transporting subsystems (bone, intestine, and kidney), Ca2+ sensi
ng, possibly by a calcium-sensing receptor, and calcium-regulating hor
mones (parathyroid hormone [PTH], calcitonin [CT], and 1,25-dihydroxyv
itamin D-3 [1,25(OH)(2)D-3]). In humans and birds, acute Ca2+ perturba
tions are handled mainly by modulation of kidney Ca2+ reabsorption and
by bone Ca2+ flow under PTH and possibly CT regulation, respectively.
Chronic perturbations are also handled by the more sluggish but econo
mic regulatory action of 1,25(OH)(2)D-3 on intestinal calcium absorpti
on. Peptide hormone secretion is modulated by Ca2+ and several secreta
gogue:;. The hormones' signal is produced by interaction with their re
spective receptors, which evokes the cAMP and phospholipase C-IP3-Ca2 signal transduction pathways. 1,25(OH)(2)D-3 operates through a cytop
lasmic receptor in controlling transcription and through a membrane re
ceptor that activates the Ca2+ and phospholipase C messenger system. T
he calciotropic hormones also influence processes not directly associa
ted with Ca2+ regulation, such as cell differentiation, and may thus a
ffect the calcium-regulating subsystems also indirectly.