Journal of Molecular Endocrinology

Overview of Ca²⁺_o homeostasis. The parathyroid CaSR senses reductions in Ca²⁺_o, which leads to a rapid rise in PTH secretion. The increased circulating PTH acts via the PTH1-receptor (PTH1R) in the kidneys and bone. The skeletal effects of PTH are to increase bone resorption, thereby releasing calcium into the extracellular fluid. In the kidney, PTH increases calcium reabsorption and stimulates the proximal renal tubular 1-α-hydroxylase (1αOHase) enzyme, which promotes the synthesis of the active 1,25-dihydroxyvitamin D3 (1,25D3) metabolite from 25-hydroxyvitamin D3 (25D3), which is the major circulating form of vitamin D. The elevated 1,25D3 acts on the intestine via the vitamin D receptor (VDR) to increase the absorption of dietary calcium. Thus, in response to hypocalcaemia, the secretion of PTH, by these direct and indirect actions leads to the restoration of normocalcaemia. The kidney CaSR senses reductions in Ca²⁺_o and promotes urinary calcium reabsorption independent of the actions of PTH. The rise in Ca²⁺_o and 1,25D3 concentrations mediated by PTH act on the parathyroid glands to induce feedback inhibition of further PTH secretion.