PTH (7-84) Human
Description
Biosynthesis and Metabolism
PTH(7-84) is generated through two primary pathways:
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Intracellular Processing: Proteases in parathyroid secretory granules cleave PTH(1-84) before secretion. Cathepsins B and H are implicated in this process .
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Peripheral Metabolism: Hepatic and renal clearance of PTH(1-84) generates C-terminal fragments, including PTH(7-84) .
The ratio of PTH(1-84) to PTH(7-84) increases in chronic kidney disease (CKD), though the fragment’s clinical significance remains debated .
Bone and Calcium Regulation
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Inhibition of Bone Resorption: PTH(7-84) reduces calcium release from bone explants and suppresses osteoclast formation in vitro. This effect is mediated by receptors distinct from PTH1R .
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Hypocalcemia Induction: In vivo studies show PTH(7-84) lowers plasma calcium and blunts the PTH(1-84) secretory response to hypocalcemia .
Paracrine/Autocrine Effects
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Regulation of PTH(1-84) Secretion: PTH(7-84) inhibits PTH(1-84) release in rats, suggesting autocrine feedback mechanisms .
Chronic Kidney Disease (CKD)
Detection Challenges
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Assay Limitations: Early immunoassays cross-reacted with PTH fragments, complicating interpretation. LC-HRMS identified PTH(7-84) as a minor component compared to other fragments (e.g., PTH(37-84)) .
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eGFR Category PTH(7-84) (pg/mL) Significance ≥60 Not detected Below detection limits in healthy individuals <15 <30 pg/mL Minimal detection even in ESKD
Receptor Interactions
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Antagonistic Effects: PTH(7-84) inhibits PTH1R-mediated cAMP production while activating alternate signaling pathways (e.g., Erk) .
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Novel Receptors: Evidence suggests PTH(7-84) binds receptors distinct from PTH1R, potentially explaining its unique biological actions .
Experimental Models
Product Specs
For reconstitution, it is recommended to dissolve the lyophilized PTH (7-84) in sterile 18 MΩ-cm H2O to a concentration of at least 100 μg/ml. Further dilutions can be made in other aqueous solutions as needed.
(a) Reverse-phase high-performance liquid chromatography (RP-HPLC) analysis.
(b) Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis.
Product Science Overview
Parathyroid hormone (PTH) is a critical regulator of calcium and phosphate metabolism in the human body. It is produced by the parathyroid glands and plays a vital role in maintaining the balance of these minerals in the blood and bones. The full-length parathyroid hormone consists of 84 amino acids, but various fragments of this hormone, including PTH (7-84), have been studied for their unique biological activities.
Parathyroid hormone (7-84) is a fragment of the full-length PTH, encompassing amino acids 7 through 84. This fragment retains some of the biological activities of the full-length hormone but also exhibits distinct properties. The full-length PTH, particularly the N-terminal region (1-34), is known for its potent effects on increasing blood calcium levels by stimulating bone resorption, increasing renal calcium reabsorption, and promoting the activation of vitamin D in the kidneys.
In contrast, PTH (7-84) has been found to have different effects. It does not significantly increase blood calcium levels and may even antagonize some of the actions of the full-length hormone. This makes PTH (7-84) an interesting subject of study for its potential therapeutic applications, particularly in conditions where modulation of PTH activity is desired without causing hypercalcemia.
Recombinant human parathyroid hormone (7-84) is produced using advanced biotechnological methods. The gene encoding the desired fragment is inserted into a suitable expression system, often using bacterial or yeast cells. These cells are then cultured under controlled conditions to produce the recombinant protein. The protein is subsequently purified using chromatographic techniques to ensure high purity and activity.
While the full-length recombinant human parathyroid hormone (1-84) has been approved for the treatment of conditions such as hypoparathyroidism and osteoporosis, the specific applications of PTH (7-84) are still under investigation. Its unique properties make it a potential candidate for conditions where selective modulation of PTH activity is beneficial. For example, it may be useful in managing certain bone disorders without the risk of increasing blood calcium levels excessively.
Ongoing research is focused on understanding the precise mechanisms of action of PTH (7-84) and its potential therapeutic benefits. Studies are exploring its effects on bone metabolism, renal function, and overall calcium and phosphate homeostasis. Additionally, researchers are investigating the potential of PTH (7-84) in combination with other treatments to enhance its efficacy and safety profile.
