Briefly discuss the functions and regulation of secretion of parathyroid hormone.

Outline:

·        Function: regulation of plasma calcium levels

·        Regulation of secretion

·        Action on kidneys, bone, intestines    

Essay:

            Parathyroid hormone (PTH) is a single-chain protein containing 84 amino acids. It is synthesized and released by the parathyroid glands. PTH is the major regulator of calcium and phosphate metabolism.

            The dominant regulator of PTH secretion is the plasma calcium level. It is actually the ionized fraction of plasma calcium that regulates PTH secretion. PTH secretion is stimulated when ionized Ca²⁺ drops below 1.3 mmol/L and is suppressed when it is greater than 1.3 mmol/L. Phosphate has no direct effects on PTH secretion. A rise in plasma phosphate levels causes an immediate fall in ionized calcium concentration, which in turn stimulates PTH secretion. Vitamin D inhibits transcription of the PTH gene, decreases PTH secretion and inhibits the proliferation of parathyroid cells.

            The paramount effect of PTH is to increase plasma calcium levels by stimulation of bone resorption, renal tubular calcium reabsorption, and cholecalciferol synthesis. At the same time, PTH decreases plasma phosphate concentration by inhibition of renal phosphate reabsorption.

            PTH receptors are present in both osteoblasts and osteoclasts. The overall effect of PTH on bone is to stimulate bone resorption and enhances the release of calcium (and phosphate) into the extracellular fluid (ECF). There are two phases of PTH action: a rapid and a late phase. During the rapid phase, PTH stimulates osteolysis by transferring calcium from the bone canalicular fluid into the osteocyte and hence out of the opposite side of the ECF. It increases the activity of the calcium pump, facilitating the outflow of Ca²⁺ from the bone and inhibits synthesis of collagen by osteoblasts, thus suppressing bone formation. During the late phase of PTH action, PTH stimulates the osteoclasts to resorb completely mineralized bone, releasing both calcium and phosphate into the ECF. The organic bone matrix is hydrolyzed by increased activity of collagenase and lysosomal enzymes. PTH also stimulates in acid phosphatase and carbonic anhydrase activity which increase formation of lactic and citric acid – the resultant decrease in pH contributes to the absorptive process.

            In the kidneys, PTH increases the reabsorption of calcium from the ascending loop of Henle and the distal tubule via the production of cAMP as a second messenger. PTH inhibits the reabsorption of phosphate in the proximal tubule and thereby increase urinary phosphate excretion, allowing deposition of the extra phosphate released by PTH-stimulated bone resorption without which dangerous precipitation of calcium-phosphate complexes might occur. PTH also inhibits the reabsorption of sodium and bicarbonate in the proximal tubule which prevents the occurrence of metabolic alkaosis due to the release of bicarbonate during the dissolution of hydroxyapatite crystals in bone. An important action of PTH is to stimulate the synthesis of cholecalciferol by inducing the key enzyme 1a-hydroxylase.

            The increase in cholecalciferol stimulates calcium absorption in the intestines by increasing the number of calcium pumps in the apical membrane and the inducing the synthesis of calcium carriers called calbindins to ferry calcium across the intestinal cell. Hence, PTH exerts an indirect effect on calcium absorption in the intestines via cholecalciferol.