Parathormone

The parathormone or parathyroidal hormone ( PTH = Parathyroïd hormone (English) or PTHi = intact PTH ) is a peptide Hormone, hypercalcémiante, secreted by the parathyroid glands.

Structure

The PTH is a protein made up of 84 amino-acid . It is produced in the form of prepro-PTH (115 amino-acids), to give the pro-PTH then PTH by successive enzymatic cleavages of sequences of amino-acids. Then, it is stored in its final form in secretary granules of the cells of parathyroid glands, to be released thereafter by exocytose. A last cleavage is done then, releasing in circulation the PTH strictly speaking and a biologically inactive fragment.

Effects

The PTH plays a key function in the regulation of the phospho-calcium metabolism, in.liaison.with the 1,25-dihydroxycholécalciférol (active form of the Vitamine D). It involves several effects on the level of the Os, the Duodénum and the Rein: it allows the retractation of the cells bordering (inactive osteoblasts) allowing fixing of osteoclasts.
  • indirect activation of the Osteoclast S, involving an increase in the osseous resorption, inducing a release of calcium and phosphate
  • stimulation of the transformation of the vitamin D into 1,25-dihydroxycholécalciférol, inducing an increase in the intestinal absorption of calcium
  • stimulation of calcium the renal reabsorption
  • inhibition of the renal phosphate reabsorption
The last effect is explained by the fact why it prevents an increase in the phosphate concentration following the osseous resorption which would delay the calcium release by the bone.

Regulation

The concentration of PTH is controlled directly by the ionized fraction of calcium (Ca2+) plasmatic. A reduction in the latter involves an increase in the secretion of the PTH, whereas an increase induces the contrary effect. A faster fall of the calcemy involves an increase more marked in the PTH, suggesting a certain capacity of anticipation of this hormone.

At the molecular level, an increase in the ionized fraction of plasmatic calcium binds to a membrane receiver with the calcium, which, via Protéines G, decreases the intracellular concentration of cyclic Adénosine monophosphate (AMPc) and increases that of Inositol triphosphate (IP3), involving an inhibition of the Exocytose granules, and thus of the secretion of PTH. The opposite takes place at the time of a reduction in the ionized fraction of plasmatic calcium.

The 1,25-dihydroxycholécalciférol inhibits the secretion of PTH per effect of negative feedback. In addition, magnesium can, like calcium, to act on the level of these receivers, but with a quite less effect, and decreases the response of the organization to the PTH. The only repercussion in practice is that a hypomagnesemy can involve a hypercalcemy.

Mode of action

The PTH binds to the level of the target cells to a transmembrane receiver coupled to a protein G, involving an increase in AMPc. This one probably involves a cascade on the level of proteins kinases, involving activation by Phosphorylation of proteins necessary to the transport of calcium and other ions.

Treatment of the osteoporosis

The teriparatide is a molecule marketed in the United States in the treatment of the osteoporosis. It obtained the LAND-MARK European under the name of Forstéo*. It is a polypeptide of 34 amino-acids corresponding to the active sequence of the human PTH.

Managed with high amount uninterrupted, the PTH has an action hypercalcémiante which involves an osseous degradation. In revanchee, managed into discontinuous, at a rate of 20  µg/jour into subcutaneous, it has an action reverses and stimulates osseous replanning, by stimulating of advantage the Ostéoblaste S that the Ostéoclaste S.

The recombining parathormone (produced by genetic engineering) was also tested with a certain effectiveness at the ménopausée woman .

See too

Random links:Lou Ferrigno | Kosh | Nigel Owens | Jacques Richard (actor) | Eugene Damas | Pinardville,_New_Hampshire