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Product Name:Parathyroid hormone from bovine parathyroid
CAS:12584-96-2
Purity:95% (HPLC)
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| Company Name: |
SIGMA-RBI
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800 736 3690 (Orders) |
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| Product Name: | Parathyroid hormone | | Synonyms: | Parathyroid Hormone 1-84, Bovine, Iodination Grade;parathyroid hormone from bovine*parathyroid gland;PARATHYROID HORMONE, BOVINE;PARATHYROID HORMONE FROM BOVINE*PARATHYR OID GLANDS;parathormone bovine;parathyroid hormone from bovine parathyroid;Parathormone bovine, PTH bovine;PTH bovine | | CAS: | 12584-96-2 | | MF: | C416H677N125O126S2 | | MW: | 9509.72 | | EINECS: | | | Product Categories: | | | Mol File: | Mol File | ![Parathyroid hormone Structure]() |
| | Parathyroid hormone Chemical Properties |
| | Parathyroid hormone Usage And Synthesis |
| Gene and mRNA | The human PTH gene is located on chromosome
11 (11p15.3-p15.1). The human PTH and chicken pth
genes comprise two introns that divide the gene into
three exons, encoding the 50
-untranslated region (UTR),
the signal peptide, the mature peptide, and the 30
-UTR. The pth gene structures of pufferfish are
similar to those of tetrapods, which include three exons
divided by two introns. | | Synthesis and release | Extracellular calcium is the primary regulator of PTH
secretion from the parathyroid gland. In mammals and
birds, the circulating levels of PTH are greatly altered
by minute changes in the blood calcium concentration. PTH secretion is modulated by the action of the
calcium-sensing receptor (CaSR), which is located in
the parathyroid gland. Under hypercalcemic conditions,
Ca2+ binding to CaSR inhibits PTH secretion. Whereas,
under hypocalcemic conditions, the receptor is not occupied by extracellular Ca2+, resulting in PTH secretion. In
addition, 1,25(OH)2D3 acts directly on the parathyroid
gland and suppresses the transcription rate of the PTH
gene. | | Receptors | The organization of the PTH1 receptor (PTH1R) gene
is highly homologous in three mammalian species,
namely the rat, human, and mouse. This gene extends
over 22 kb and contains at least 15 exons and 14 introns.
The human gene was mapped to chromosome 3p21.1-
p22. Both PTH and parathyroid hormone-related protein
(PTHrP) bind to the PTH1R. As both peptides signal
through the same receptor, it is also called the PTH/
PTHrP receptor. In contrast, the PTH receptor type 2
(PTH2R) is not activated by PTHrP but by PTH and a
tuberoinfundibular peptide of 39 amino acids (TIP39). TIP39 is known as a ligand of PTH2R, although the similarity of sequence between TIP39 and PTH is low. In addition to PTH1R and PTH2R, zebrafish
and other teleosts possess a third receptor, PTH3R, which may be derived by the duplication of
PTH1R. PTHRs share the same basic structure (seven transmembrane domains) with that of the class B G-protein
coupled receptor (GPCR) superfamily. A defining feature
of the class B receptors is the relatively long extracellular
N-terminal domain, which comprises approximately 150
amino acids and is important for ligand binding. The
presence of six cysteine residues that are strictly conserved within the N-terminal domain of all class
B GPCRs suggests that three disulfide linkages are present and are of critical importance. Kd in human kidney
plasma membrane, canine kidney plasma membrane,
and chick bone cell membrane is 1–5 nM. | | Agonists and Antagonists | The complete molecule is not essential to exert a biological effect. The N-terminal fragments of PTH and
PTHrP, comprising amino acids 1–34, have biological
activities similar to those of the complete molecules. PTH (1–14) and PTH (1–21) analogs show high-affinity
binding and efficient activation of the PTH1R. [Leu11, D-Trp12] PTHrP (7–34) and [Ile5
, Trp23] PTHrP
(5–36) bind with high affinity to PTH1R but are devoid of signaling activity. The PTH2R agonist, TIP39, binds
efficiently to the PTH1R but does not activate it, and thus
functions as a weak antagonist at this receptor. | | Description | First hormone isolated from the parathyroid gland to have
hypercalcemic action. PTH is a drug target for hypoparathyroidism and osteoporosis. The presence of PTH in the parathyroid gland was
reported in 1925. It was isolated in 1970 from bovine
parathyroid glands. It was believed that PTH was absent
in fish because the parathyroid gland is thought to appear
when ancestral amphibians evolved. However, PTH was
first identified from the fugu genome database in 2003, and thereafter the existence of PTH has been established
in fish. | | Chemical Properties | 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. | | Physical properties | Mammalian PTHs: Mr. 9500. It is soluble in water and
stable in a solution at pH 4.5. PTH in the collected blood is
relatively unstable and hydrolyzes easily during storage.
It is recommended that blood samples for PTH measurement should be taken using tubes containing EDTA and
plasma should be separated within 24 h. | | Uses | 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. | | Brand name | Paroidin (Parke-Davis). | | 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 | | Clinical Use | Treatment of chronic hypoparathyroidism | | Clinical Use | diagnose a variety of calcium metabolic disorders, such
as hyperparathyroidism, hypoparathyroidism, hypercalcaemia of malignancy, and chronic renal failure.
The skeletal actions of PTH are dependent on the pattern of its administration.12 Intermittent exposure to PTH
leads to a net increase in bone formation, whereas its continuous administration produces bone loss. Thus, the
bone anabolic capability of PTH strictly depends upon
its administration producing a transient peak level in
plasma. PTH is used for osteoporosis therapy because of its
ability to increase osteoblastogenesis and osteoblast survival. Furthermore, PTH is involved in the proliferation
and differentiation of chondrocytes because mutations in
the PTH1R have been identified in Jansen-type metaphyseal chondrodysplasia and Blomstrand-type lethal
chondrodysplasia. | | Drug interactions | Potentially hazardous interactions with other drugs
Bisphosphonates: reduction of calcium-sparing effect
with alendronate - avoid. | | Metabolism | Parathyroid hormone is metabolised in the liver and to a
lesser degree in the kidney. Parathyroid hormone is not
excreted from the body in its intact form. Circulating
carboxy-terminal fragments are filtered by the kidney, but
are subsequently broken to even smaller fragments during
tubular reuptake.
Parathyroid hormone is efficiently removed from the blood
by a receptor-mediated process in the liver and is broken
down into smaller peptide fragments. The fragments derived
from the amino-terminus are further degraded within the
These carboxy-terminal fragments are thought to play a role
in the regulation of parathyroid hormone activity | | Structure and conformation | PTH is a single-chain nonglycosylated peptide. In
humans, PTH is synthesized as a 115-aa precursor polypeptide. The signal peptide is cleaved, and the mature
peptide is packed in secretory vesicles and then secreted
as an 84-aa peptide . Chicken PTH consists of
88 aa with a striking similarity to the mammalian PTHs in
the N-terminus. In the zebrafish and pufferfish, two PTH genes and one PTH-like protein gene have
been discovered. In addition, the elephant shark has
PTH1 and PTH2, although questions are left unanswered about the classification of these hormones in the
PTH/PTHrP family. The mature PTH in mammals comprises an 84-aa peptide, the sequence of which varies in nonmammalian vertebrates. Among teleost fish, humans, and
chickens, the amino acid identity of mature PTHs is
around 20%–25% and the sequence similarity is close to
40%. However, high sequence conservation is observed
among the first 34N-terminal amino acid residues of all
PTHs.
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| | Parathyroid hormone Preparation Products And Raw materials |
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