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.
용도
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).
Indications
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.
Biosynthesis
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.
Biological Functions
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.
Pharmaceutical Applications
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.
Mechanism of action
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
