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Parathyroid Hormone Family Related Drug Discovery Products

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The circulating hormone known as parathyroid hormone (PTH) is made up of 84 amino acids. It is produced in the parathyroid glands and primarily impacts the kidney and bones to maintain proper extracellular calcium levels. The primary parathyroid gland cells secrete PTH, primarily in reaction to low extracellular calcium levels but also in response to elevated extracellular phosphate levels. The suppression of PTH release from the parathyroid gland in response to high extracellular calcium levels is an unusual trait for an endocrine tissue.

Parathyroid Hormone Family. Fig.1. Parathyroid Hormone Family. (Gensure, 2005)

Creative Biolabs can offer high-quality parathyroid hormone family in vitro assays and related products to contribute to the success of drug discovery:

Overview of Parathyroid Hormone Family

Due to its similar affinity for both PTH and PTHrP, PTH1R is also known as the PTH/PTHrP receptor. PTH2R was later discovered in humans, showing a preference for PTH over PTHrP as a ligand. The PTH/PTHrP receptor's signaling through the stimulatory G-protein Gαs, which in turn triggers the activation of protein kinase A and boosts cAMP synthesis, sets off a series of intracellular events. It has also been shown that the receptor can directly interact with sodium/hydrogen exchanger regulatory factor (NHERF) 1 or 2 by way of the psd95, disks-large, ZO-1 (PDZ), and C-terminal intracellular tails of the receptor. The numerous physiological roles of the PTH/PTHrP receptor in multiple organs and its responsiveness to two different ligands may be related to the biological significance of these alternative, noncAMP signaling pathways. PTH/PTHrP receptor mutant (DSEL), which induces cAMP synthesis normally but does not result in inositol trisphosphate generation, has been used to study the impact of phospholipase C signaling.

Receptor signaling. Fig.2. Receptor signaling. (Polyzos, 2015)

Parathyroid Hormone Family Drug Discovery

It is well established that pulsatile administration of PTH causes an increase in bone production, whereas persistent elevation of PTH levels causes bone degradation. The clinical usage of PTH(1-34) in the treatment of osteoporosis is now supported by this anabolic action of PTH. Unfortunately, PTH, like the majority of short bioactive peptides, is ineffective when taken orally; as a result, daily injections are required to have an anabolic impact. PTH antagonists may be used to treat humoral hypercalcemia of malignancy syndrome or hyperparathyroidism. It is conceivable that inverse agonists could be employed to treat Jansen's chondrodysplasia and related conditions.

References

  1. Gensure, R.C.; et al. Parathyroid hormone and parathyroid hormone-related peptide, and their receptors. Biochemical and biophysical research communications. 2005, 328(3): 666-678.
  2. Polyzos, S.A.; et al. Investigational parathyroid hormone receptor analogs for the treatment of osteoporosis. Expert Opinion on Investigational Drugs. 2015, 24(2): 145-157.

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