Parathyroid hormone PTH

Parathyroid hormone is an 84 amino acid polypeptide, with a molecular weight of9500. The molecule has no disulphide bridges. Biological activity is confined to the NH2-terminal 34 amino acid sequence. It is encoded for on chromosome 11. The serum level ranges from 10-60 pg/ml and the circulating half-life is 2-4 minutes.

It is secreted by parathyroid chief cells as a prepro-PTH, a 115 amino acid precursor. A 25 amino acid hydrophilic leader peptide is cleaved from the -NH2 terminus to yield a prohormone. Further cleavage of a basic, -NH2-terminal hexapeptide yields the mature 84 amino acid hormone. Parathyroid hormone is cleaved at the 33-34 and 36-37 positions in the liver and kidneys to yield an amino terminal and a carboxyl terminal fragment.

Parathyroid hormone maintains the plasma ionised calcium level, the PTH level being controlled by a negative feedback mechanism. The calcium sensing receptor is a glycoprotein with molecular weight of 500 000 and is located on the parathyroid cell surface. Magnesium is required for PTH release and for its effects on target tissues. Serum PTH levels show a diurnal circadian variation. For the correct interpretation of the significance of serum levels, simultaneous measurement of serum calcium and phosphate concentrations is required.

It has a direct effect on bone and renal tubules and an indirect effect on small intestine. Parathyroid hormone binds to plasma membrane G-protein-coupled receptors on target cells in bone and the kidneys, where they are concentrated at the basolateral surface of the cortical thick ascending limb of the loop of Henle. The calcium-sensing receptor (CSR) is a 1079 amino acid membrane protein, with seven a-helical transmembrane domains, an extracellular domain and an intracellular carboxyl-terminal G-protein-binding domain. The extracellular domain binds Ca2+ and Mg2+. The calcium-sensing receptor detects the serum calcium concentration, and determines the set point for the serum PTH concentration.

Parathyroid hormone increases bone resorption (osteolysis) by increasing the numbers and activity of osteoclasts, and by increasing calcium transport from bone to the extracellular fluid. It increases proximal renal tubular reabsorption of a calcium and reduces tubular reabsorption of phosphate (cyclic AMP mediated). u

Parathyroid hormone stimulates renal hydroxylation of 25-hydroxy vitamin 3

D3 to 1,25-dihydroxyvitamin D3, which increases intestinal calcium absorption a by inducing a calcium-binding protein in the duodenal and jejunal mucosae. i

There is no direct effect on intestine. Parathyroid hormone acts synergistically 3 with calcitriol to absorb calcium and phosphate.

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