Parathyroid hormone

• OMIM: 168450
• UniProt: P01270
• MGI: 97799

Parathyroid hormone and parathyroid hormone (PTH ) is a peptide hormone consisting of 84 amino acids, which is formed in the main cells of parathyroid gland. The main function of the parathyroid hormone is to increase the calcium concentration in blood plasma.

A decrease this concentration induces increased PTH secretion. Various causes may be responsible ( hyperparathyroidism and hypoparathyroidism ) for a too high or too low a content of the blood of PTH. Changes in PTH gene that lead to hypoparathyroidism, are known.

Biosynthesis

Parathyroid hormone is used as a pre-pro- hormone (115 amino acids) synthesized by membrane bound ribosomes and cotranslationally with elimination of the amino-terminal signal sequence (pre- sequence) is processed, so that pro- parathyroid hormone ( 90 amino acids ) forms. By processing in the Golgi apparatus the finished parathyroid hormone is produced (see translation).

Reduction

The parathyroid hormone has a half -life of a few minutes, and proteolytic degradation both in the parathyroids itself as well as in the liver and the kidney. Since only a very small amount of the parathyroid hormone is responsible for the biological activity resulting from the proteolysis partial intermediates, which also have biological activity, and in the blood can be detected.

Mechanism and control of secretion

PTH secretion is reciprocally regulated in dependence on the plasma calcium concentration ( ionized fraction), that is, a rise above the normal value inhibits PTH secretion (negative feedback). At a concentration of 1 mmol / l plasma ionized calcium, the maximum PTH secretion is reached, and 1.25 mmol / l of a minimum of 10% secretion. A rise above 1.25 mmol / l therefore leads to no further reduction in PTH secretion ( basal secretion activity ).

For this regulatory mechanism in 1993 is discovered calcium -sensitive receptor responsible. It is a G -protein coupled receptor which when activated uses the Inositolphosphatweg by the ligand (high calcium concentration ) in the passage which leads to the increase in the cytoplasmic inositol triphosphate and diacylglycerol concentration. Probably inhibit adenylyl cyclase, inositol triphosphate, such that the cytoplasmic cAMP concentration decreases and thereby decreases the secretion of parathyroid hormone.

Effects

Induction of osteolysis

PTH leads indirectly to the maturation and activation of osteoclasts, and thus in a calcium phosphate mobilization from the bone tissue.

Osteoclasts themselves have no PTH receptors. Upon binding of parathyroid hormone to the receptors of osteoblasts of osteoblasts is incorporated, inter alia, of RANK ligand in the plasma membrane. RANKL interacts with RANK, a membrane receptor which is expressed upon activation of osteoclasts and promotes the osteoclastogenesis. A negative calcium balance of the bone, however, occurs only in pathologically elevated PTH concentrations.

Inhibition of phosphate reabsorption

PTH inhibits renal phosphate reabsorption ( reuptake ) by the proximal tubule cells in the proximal tubule and increases calcium absorption ( recovery) in the distal tubule. Phosphate is primarily a sodium - phosphate cotransporter ( NPT2 ) transported from the primary back in the renal epithelial cells of the proximal tubule. From there, phosphate passes back into the blood. When sufficient phosphate is absorbed from the food, inhibits parathyroid hormone phosphate reabsorption in the kidney.

The inhibition takes place in that is internalized under the action of the parathyroid hormone NPT2 cotransporter and degraded in lysosomes. Thus, the number of active transport molecules in the luminal cell membrane is reduced. This process is initiated by the binding of PTH to its receptor PTHR1 and subsequent increase in the cytosolic concentration of the second messenger cAMP with subsequent activation of protein kinase A. Although the binding of PTH to PTHR1 by increasing the IP3 concentration also leads to an activation of protein kinase C, although it could be shown that this is for the acute regulation of available NPT2 cotransporter of minor importance.

The phosphate level in the blood drops, then, as more phosphate is excreted in the urine. This makes sense, as this again in the blood may be more free ionized calcium (which with this in the kidney forms a sparingly soluble complex at too high phosphate concentration, and fails to so-called Kalkniere leads ).

Induction of biosynthesis of calcitriol

In other PTH increases the activity of 1α -hydroxylase, the key enzyme of calcitriol biosynthesis (vitamin D3) that is mainly localized in the kidney, and with the aid of (vitamin D3), PTH increases the enteral calcium absorption in the terminal ileum.

Clinic

Blood value (reference range ):

• Parathyroid hormone in serum: 12-72 ng / l and 1.5-6.0 pmol / l

Increased blood levels ( hyperparathyroidism ):

• Degenerate parathyroid glands (adenomas or carcinomas rarely ) not subject to the calcium-dependent Sekretionssteuerung. It comes to an uncontrolled increase in parathyroid hormone levels ( primary hyperparathyroidism ), thereby contributing to hypercalcemia.

• On hypocalcaemia due to kidney liver or bowel diseases, the body reacts with an increased secretion of parathyroid hormone ( secondary hyperparathyroidism ) by hyperplasia of the parathyroid glands.

• If the cause of secondary hyperparathyroidism suddenly treated (eg kidney ) remains the basal secretion of parathyroid hormone due to the increased reactive Epithelkörperchenhyperplasie (tertiary hyperparathyroidism ). Consequence is a hypercalcemia.

• In the course of malignant diseases ( lung cancer, breast cancer, prostate cancer, multiple myeloma ) may occur paraneoplastic hypercalcemia. The abnormal cells form a parathyroid hormone related peptide (PTHrP ), which acts as parathyroid hormone ( Pseudohyperparathyreoidism ).

Decreased blood ( hypoparathyroidism ):

• After thyroid surgery, Epithelkörperchenadenomentfernung or autoimmune parathyroid hormone deficiency can occur. It comes to the lowering of calcium levels and subsequently lead to hypocalcemic tetany. The constellation hypocalcemia, hypomagnesemia, and hyperphosphatemia with normal renal function ( creatinine ) and exclusion of malabsorption ( albumin level ) indicates a malfunction of the parathyroid glands. Decreased blood levels of parathyroid hormone proves the diagnosis of hypoparathyroidism.