12584-96-2

Basic information

• 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 NO: 12584-96-2
• Molecular Formula: C416H677N125O126S2
• Molecular Weight: 9509.72
• Mol File: 12584-96-2.mol
• Article Data: 0

Chemical Properties

• Appearance: /
• Storage Temp.: −20°C
• CAS DataBase Reference: PARATHYROID HORMONE(CAS DataBase Reference)
• NIST Chemistry Reference: PARATHYROID HORMONE(12584-96-2)
• EPA Substance Registry System: PARATHYROID HORMONE(12584-96-2)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 12584-96-2(Hazardous Substances Data)

Usage

Description

PARATHYROID HORMONE (PTH) is a single-chain polypeptide hormone composed of 84 amino acid residues, with a molecular weight of 9,500. It is the first hormone isolated from the parathyroid gland and is known for its hypercalcemic action. PTH plays a crucial role in regulating blood calcium levels, bone metabolism, and is a drug target for hypoparathyroidism and osteoporosis. PTH is soluble in water and stable at pH 4.5, but it is relatively unstable in collected blood samples and hydrolyzes easily during storage.

Uses

1. Used in Pharmaceutical Industry:
PARATHYROID HORMONE is used as an antiosteoporotic for the treatment of osteoporosis. It helps in the regulation of bone metabolism and blood calcium levels, making it a potential therapeutic agent for bone and mineral diseases and disorders.
2. Used in Diagnostic Industry:
PARATHYROID HORMONE is used as a diagnostic aid for conditions such as pseudohypoparathyroidism and hypocalcemia. Its measurement in blood samples can help in the diagnosis and monitoring of these conditions.
3. Used in Clinical Trials:
PARATHYROID HORMONE has been used in clinical trials as a therapeutic agent for osteoporosis. The N-terminal fragments of PTH and PTHrP, comprising amino acids 1–34, have biological activities similar to those of the complete molecules, making them potential candidates for drug development.
4. Used in Research and Development:
PARATHYROID HORMONE and its analogs, such as PTH (1–14) and PTH (1–21), show high-affinity binding and efficient activation of the PTH1R. These analogs are being studied for their potential applications in the treatment of various bone-related conditions.
Brand Name:
Paroidin (Parke-Davis) is a brand name for PARATHYROID HORMONE.
Agonists and Antagonists:
The N-terminal fragments of PTH and PTHrP, comprising amino acids 1–34, have biological activities similar to those of the complete molecules. Some analogs, such as [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.

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.

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

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.