Parathyroid Hormone, Recombinant, Human (PTH) (1-34)

Polypeptide hormones secreted by the parathyroid glands, which promote release of calcium from bone to extracellular fluid by activating osteoblasts and inhibiting osteoclasts, indirectly promote increased intestinal absorption of calcium and promote renal tubular reabsorption of calcium and increased renal excretion of phosphates. It is a major regulator of bone metabolism. Secretion of parathyroid hormone increases when the level of calcium in the extracellular fluid is low. Its action is opposed by calcitonin. Parathyroid hormone (PTH), or parathormone, is secreted by the parathyroid glands as a polypeptide containing 84 amino acids. It acts to increase the concentration of calcium (Ca2+) in the blood, whereas calcitonin (a hormone produced by the parafollicular cells (C cells) of the thyroid gland) acts to decrease calcium concentration. PTH acts to increase the concentration of calcium in the blood by acting upon parathyroid hormone receptor in three parts of the body. PTH half-life is approximately 4 minutes. PTH enhances the release of calcium from the large reservoir contained in the bones. Bone resorption is the normal destruction of bone by osteoclasts, which are indirectly stimulated by PTH. Stimulation is indirect since osteoclasts do not have a receptor for PTH; rather, PTH binds to osteoblasts, the cells responsible for creating bone. Binding stimulates osteoblasts to increase their expression of RANKL, which can bind to osteoclast precursors containing RANK, a receptor for RANKL. The binding of RANKL to RANK stimulates these precursors to fuse, forming new osteoclasts which ultimately enhances the resorption of bone.\n\nIn the kidney, PTH enhances active reabsorption of calcium and magnesium from distal tubules and the thick ascending limb. As bone is degraded both calcium and phosphate are released. It also greatly increases the excretion of phosphate, with a net loss in plasma phosphate concentration. By increasing the calcium:phosphate ratio more calcium is therefore free in the circulation. PTH enhances the absorption of calcium in the intestine by increasing the production of activated vitamin D. Vitamin D activation occurs in the kidney. PTH up-regulates 25-hydroxyvitamin D3 1-alpha-hydroxylase, the enzyme responsible for 1-alpha hydroxylation of 25-hydroxy vitamin D, converting vitamin D to its active form (1,25-dihydroxy vitamin D). This activated form of vitamin D increases the absorption of calcium (as Ca2+ ions) by the intestine via calbindin. PTH was one of the first hormones to be shown to use the G-protein, adenylyl cyclase second messenger system. Normal total plasma calcium level ranges from 8.5 to 10.2mg/dL (2.12mmol/L to 2.55mmol/L).\n\nRecombinant Human PTH is a single, non-glycosylated, polypeptide chain containing 34 amino acids and having a molecular mass of 4117.8 Dalton.\n\nSequence:\nThe sequence of the first five N-terminal amino acids was determined and was found to be Ser-Val-Ser-Glu-Ile.\n\nDimers and Aggregates:\n(same/less than) 1% as determined by silver-stained SDS-PAGE gel analysis.\n\nBiological Activity:\nrHuPTH is fully biologically active when compared to standards. The activity calculated by UMR106 cell/cAMP method corresponding to a specific activity of 1.0 x 10e4 Units/mg.\n\nEndotoxin:\n(same/less than) 0.1ng/ug (IEU/ug) of rHuPTH.\n\nProtein Content:\nProtein quantitation was carried out by two independent methods: \n1. UV spectroscopy at 280nm. \n2. Analysis by RP-HPLC, using a calibrated solution of PTH as a Reference Standard.\n\nReconstitution:\nReconstitute the lyophilized rHuPTH in sterile 18MOmega-cm H2O not less than 100ug/ml, which can then be further diluted to other aqueous solutions.\n\nStorage and Stability:\nLyophilized powder may be stored at 4 degrees C for short-term only. Reconstitute to nominal volume by adding sterile dH2O and store at -20 degrees C. Reconstituted product is stable for 12 months at -20 degrees C. For maximum recovery of product, centrifuge the original vial prior to removing the cap. Further dilutions can be made in assay buffer.

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SPECIFICATIONS

Catalog Number

P3109-27

Size

100ug

Form

Supplied as a lyophilized powder in sodium citrate, sodium chloride, citric acid, EDTA-Na2, Tween 80, mannitol.

Purity

(same/more than) 95% by RP-HPLC, FPLC, or reducing/non-reducing SDS-PAGE Silver Stain. Chromatographically purified.

References

1. Parathyroid hormone venous sampling before reoperative surgery in renal hyperparathyroidism: comparison with noninvasive localization procedures and review of the literature. Seehofer D, Steinmuller T, Podrabsky P, Schindler R, Arch Surg 2004 Dec;139(12):1331-8 2. Immediate and medium-term results of intraoperative parathyroid hormone monitoring during video-assisted parathyroidectomy. Maweja S, Sebag F, Giorgi R, Arch Surg 2004 Dec;139(12):1301-3 3. Fibroblast growth factor 23, parathyroid hormone, and 1alpha,25-dihydroxyvitamin D in surgically treated primary hyperparathyroidism. Tebben PJ, Singh RJ, Kumar R, Mayo Clin Proc 2004 Dec;79(12):1508-13 4. Effect of intermittent administration of human parathyroid hormone on bone mineral density and arthritis in rats with collagen-induced arthritis. Fukata S, Hagino H, Yamane I, Arthritis Rheum 2004 Dec;50(12):4060-9 5. [New interventions controlling parathyroid hormone] Tominaga Y, Clin Calcium 2004 Jan;14(1):51-5 6. [Extraskeletal actions of parathyroid hormone in hemodialysis patients] Okuno S, Clin Calcium 2004 Jan;14(1):27-31.