ПАРАТИРОИДНЫЙ ГОРМОН

PTH is a single-chain polypeptide composed of 84 amino acid residues that is devoid of disulfide bonds and has a molecular weight of 9500. Biological activity of the human hormone resides primarily in the amino terminal end of the protein (i.e., amino acids 1–34).This portion of PTH has full biological activity both in vivo and in vitro. Synthetic fragments of the 1-34 portion of the PTH molecule have been synthesized. A paraneoplastic hormone, PTH related peptide (PTHrP) has been identified, isolated, and synthesized. PTHrP is structurally homologous to the amino terminal portion of PTH and interacts with the PTH receptor in bone and kidney. This hormone is responsible for hypercalcemia in certain forms of malignancy. It has been used as a therapeutic agent in osteoporosis in some clinical trials.

Treatment of osteoporosis, as an antiosteoporotic, in the treatment of bone and mineral disease and disorders, bone metabolism regulator, blood calcium regulator, and as a diagnostic aid (pseudohypoparathyroidism; hypocalcemia).

PTH is secreted from the parathyroid glands in response to a low plasma concentration of ionized (free) calcium. PTH immediately causes the transfer of labile calcium stores from bone into the bloodstream. PTH increases rates of dietary calcium absorption by the intestine indirectly via the vitamin D₃ system activation of enterocyte activity.Within the kidney, PTH directly stimulates calcium reabsorption and a phosphate diuresis.

Plasma calcium concentration is the principal factor regulating PTH synthesis and release. The increase in PTH synthesis and secretion induced by hypocalcemia is believed to be mediated through activation of parathyroid gland adenylyl cyclase and a subsequent increase in intracellular cyclic adenosine monophosphate (cAMP).
Formation of PTH begins with the synthesis of several precursor molecules. PreproPTH is the initial peptide that is synthesized within the parathyroid gland, and it serves as a precursor to both proPTH and PTH. PreproPTH is formed within the rough endoplasmic reticulum, transported into the cisternal space, and then cleaved to form proPTH. The proPTH polypeptide is transported into the cisternal space, where another proteolytic cleavage occurs, forming PTH.

Parathyroid hormone (PTH) is biosynthesized as a 115-amino-acid preprohormone in the rough endoplasmic reticulum of the parathyroid gland and is cleaved to the prohormone (84 amino acids) in the cisternal space of the reticulum. The active hormone is finally produced (34 amino acids; molecular weight, 9,500 dalton) in the Golgi complex and is stored in secretory granules in the parathyroid gland. This gland is exquisitely sensitive to serum calcium concentrations and is able to monitor these levels via calcium-sensing receptors (CaSR). These cell surface receptors help cells to react to micromolar changes in the concentration of ionized calcium in the serum. Binding of calcium to these receptors facilitates activation of phospholipase C and, ultimately, inhibition of PTH secretion. The relatively short-acting PTH is secreted from the parathyroid gland chief cells in response to a hypocalcemic state and serves to oppose the hormonal effects of calcitonin.

PTH (parathyroid hormone), which are called calciotropic hormones. PTH controls the serum plasma level of Ca²⁺ by regulating the re-absorption ofCa²⁺ in the nephron, stimulating the uptake of Ca²⁺ from the gut and releasing Ca²⁺ from the bones which act as a reservoir.

Unlike calcitonin, the biological activity of PTH resides solely in residues 1 to 34 in the amino terminus. Parathyroid hormone decreases renal excretion of calcium, indirectly stimulates intestinal absorption of calcium, and in combination with active vitamin D, promotes bone resorption by a complex, unknown mechanism, thereby elevating serum calcium concentrations. In addition, the secretion of PTH stimulates the biosynthesis and release of the third hormone associated with calcium homeostasis, vitamin D. When serum calcium concentrations are high, the release of PTH is inhibited