PTH acts to increase the concentration of calcium in the blood in three ways. It enhances the release of calcium from the large reservoir contained in the bones, enhances reabsorption of calcium from renal tubules; and enhances the absorption of calcium in the intestine by increasing the production of vitamin D and upregulating the enzyme responsible for 1-alpha hydroxylation of 25-OH vitamin D converting vitamin D to its active form (1,25-OH vitamin D) which effects the actual absorption of calcium by the intestine.
PTH also acts to decrease the concentration of phosphate in the blood, primarily by reducing reabsorption in the proximal tubules of the kidney. The decreased phosphate enhances bone demineralization.
Increased calcium concentration in the blood acts (via feedback inhibition) to decrease PTH secretion by the parathyroid glands. This is achieved by the activation of calcium-sensing receptors located on parathyroid cells.
Bone resorption
Bone resorption is the normal destruction of bone by osteoclasts, which are indirectly stimulated by PTH. Stimulation is indirect since osteoclasts do not have a receptor for PTH; rather, PTH binds to osteoblasts, the cells responsible for creating bone. Binding stimulates osteoblasts to increase their expression of RANKL, which can bind to osteoclast precursors containing RANK, a receptor for RANKL. The binding of RANKL to RANK stimulates these precursors to fuse, forming new osteoclasts which ultimately enhances the resorption of bone.
Syndromes
Excessive PTH secretion is known as hyperparathyroidism, and is often the result of a benign parathyroid tumor (primary hyperparathyroidism) that loses its sensitivity to circulating calcium levels. In chronic renal failure secondary hyperparathyroidism can result.
PTH can be measured in the blood in several different forms: intact PTH; N-terminal PTH; mid-molecule PTH, and C-terminal PTH, and different tests are used in different clinical situations.
