Inquiry Basket
Loading ......
Parathyroid hormone (PTH) is a polypeptide hormone secreted by the main cells of the parathyroid gland and consists of 84 amino acids. The human PTH gene is a single-copy gene located on the short arm of chromosome 11. Its main function is to regulate the body's calcium and phosphorus balance. The acute effect of PTH in the body is to increase bone resorption, but the continued increase in its blood circulation level will accelerate bone formation and bone resorption. Research shows that PTH is the main determinant of human bone turnover rate and plays an important role in the occurrence, prevention and treatment of osteoporosis. PTH is one of the main bone formation-promoting drugs currently used in clinical practice. It can effectively increase bone mass and treat osteoporosis, osteoporotic fractures, compression fractures, and loosening of joint prostheses.
Figure 1. Transcription factors that determine parathyroid development power PTH expression. (Naveh-Many T, et al.; 2018)
The transcription and secretion of PTH are regulated by multiple factors. Extracellular calcium ions (Ca2+) levels are the primary physiological regulator of parathyroid hormone secretion. Studies have shown that parathyroid cells have calcium-sensitive receptors (CaSR) on their surfaces, which enable them to sense small changes in extracellular Ca2+ concentration and thereby rapidly regulate the secretion of PTH. 1α, 25(OH)2D3, fibroblast growth factor (FGF-23) and estrogen can affect the expression and secretion of parathyroid hormone through their corresponding cell receptor systems. In addition, at low blood calcium concentrations, magnesium (Mg) can reduce parathyroid hormone secretion by upregulating CaSR, vitamin D receptor (VDR), and FGF23/Klotho system. The latest research shows that the zinc finger transcription factor Gata3 gene can combine with the transcription regulatory genes Gcm2 and MafB to jointly activate the transcription of PTH. In recent years, as people's research on parathyroid hormone continues to deepen, it is particularly important to systematically summarize the research on the expression regulation of this gene. This article briefly reviews the research progress on PTH gene expression regulation in recent years, with a view to providing a useful reference for research and applications in this field.
CaSR is a cell surface protein containing 1078 amino acid residues and belongs to the third superfamily of G protein-coupled receptors. Since CaSR was isolated and cloned from bovine parathyroid cells, researchers have successively identified the expression of CaSR in a variety of tissues and cells, including kidneys, intestines, bones and other tissues and organs that are directly involved in calcium homeostasis in the body, as well as nerves system, stomach, taste tissue, myocardium and other tissues and organs that are not directly involved in calcium homeostasis, and the function of CaSR in the latter is not yet clear.
Studies have found that CaSR in the parathyroid glands and kidneys plays a crucial role in regulating calcium homeostasis in the body. It can convert small changes in blood calcium concentration into the secretion of PTH in the parathyroid glands and the excretion of Ca2+ in the kidneys. It is well known that the Ca2+ concentration in plasma is regulated by PTH to a large extent. PTH can act on the kidneys and bones, thereby increasing plasma Ca2+ levels, and the increase in plasma Ca2+ concentration will in turn inhibit the secretion of PTH. Therefore, parathyroid cells appear to be unusual in that they are able to sense weak changes in extracellular Ca2+ and thereby change PTH secretion in a timely manner. Studies have found that CaSR is expressed on the surface of parathyroid cells, which allows the cells to detect and respond to small changes in extracellular Ca2+. Extracellular Ca2+ flows into cells through ion channels on the cell membrane, which increases the calcium concentration in parathyroid cells, thereby inhibiting the secretion of PTH.
Vitamin D3 is a prohormone produced by 7-dehydrocholesterol in the skin after ultraviolet irradiation. It has no physiological activity. Vitamin D3 in animals must be hydroxylated twice in the liver and kidneys to convert it into its active form 1α, 25 (OH)2D3 can exert its best biological activity. It is well known that 1α, 25 (OH)2D3 and PTH play key roles in maintaining calcium metabolism balance and bone metabolism balance. Studies have shown that 1α-hydroxylase is the key enzyme that converts 25(OH)D3 into 1α, 25 (OH)2D3. PTH can induce the transcription of the 1α-hydroxylase gene in the kidney, thereby accelerating 1α, 25 (OH)2D3 generation. Conversely, excess 1α, 25 (OH)2D3 leads to transcriptional inhibition of 1α-hydroxylase in the kidney and PTH in the parathyroid gland.
The function of vitamin D is achieved by activating VDR in the cell nucleus. VDR is essentially a ligand-dependent cis-activating transcriptional regulator. After binding to 1α, 25 (OH)2D3, it recruits a variety of transcriptional regulators to form a transcription machine, thereby regulating the transcriptional expression of target genes. Studies have shown that the reduced expression of VDRＲ in parathyroid glands is closely related to the pathogenesis of hyperparathyroidism and highly hyperplastic parathyroid adenoma. Genetic association studies have shown that alleles b, a, and T of VDR will reduce the mRNA level of VDR and enhance the resistance of PTH secretion to Ca2+, thereby increasing the risk of primary hyperparathyroidism. 1α, 25 (OH)2D3 can inhibit PTH secretion and thyroid cell proliferation through nuclear VDR. The researchers used a highly specific and sensitive immunohistochemical method based on D-6 antibody to detect the expression of VDR in rat parathyroid epithelial cells. Studies have confirmed that there are negative vitamin D response elements (nVDRE) in the promoters of human PTH (hPTH) gene, rat PTH (rPTH) gene and human PTH-related protein (PTHrP) gene. The VDR interactive repressor (VDIR) is a bHLH-type activator that can bind to the nVDRE of the promoter of the target gene negatively regulated by the vitamin D receptor together with the histone acetyltransferase coactivator, thereby activating Transcription of this gene. Vitamin D-activated VDR binds to nVDRE through VDIR, dissociates the histone acetyltransferase coactivator, and recruits histone deacetylase corepressors, thereby inhibiting the transcription of target gene (such as PTH) promoters.
FGF-23 is a diuretic phosphate hormone secreted by osteoblasts. Its main function is to increase renal phosphate excretion and inhibit renal 1α-hydroxylase activity, thereby inhibiting the biosynthesis of 1α, 25 (OH)2D3. An important feature of autosomal dominant hypophosphatemic rickets (ADHR) is renal phosphate loss. The researchers used positional cloning methods to identify 37 candidate genes for ADHR. Further analysis showed that mutations in the FGF-23 gene can cause ADHR. Overexpression of FGF-23 can not only inhibit osteoblast differentiation and matrix mineralization, but also inhibit the expression and secretion of PTH. Mice transgenic for FGF-23 driven by the β-actin promoter develop biochemical and skeletal phenotypes of ADHR, neoplastic osteomalacia, or those disease caused by significant increases in mutant or intact FGF-23. The blood phosphorus and 1α, 25 (OH)2D3 concentrations of this transgenic mouse have decreased, which should increase the secretion of PTH, but in fact the level of PTH is reduced. Some researchers believe that transgenic overexpression of FGF-23 will increase the secretion of PTH in mice, presumably due to the decrease in 1α, 25 (OH)2D3 in the serum. Studies have confirmed that Klotho, the co-receptor of FGF-23, is expressed in the parathyroid glands. FGF-23 can act on parathyroid cells through the FGFRs/Klotho receptor system and the MAPK pathway, thereby effectively inhibiting the expression and secretion of parathyroid hormone. This indicates that the parathyroid gland is a new target organ of FGF-23. In addition to enhancing the renal excretion of phosphate and inhibiting the production of 1α, 25 (OH)2D3, it can also directly act on the parathyroid gland, thereby reducing serum PTH levels.
Past studies have limited understanding of the regulatory mechanism between estrogen and PTH, and have mainly focused on the effects of estrogen on osteoclast and osteoblast activity. It is known that estrogen can inhibit bone resorption, reduce bone metabolism and maintain bone mass. Understanding the effects of estrogen on osteoclast and osteoblast activity is critical for the treatment of postmenopausal bone osteoporosis. Studies have shown that estrogen can block the PKA pathway through the estrogen receptor (ER), thereby inhibiting the formation of osteoclasts induced by PTH. Insulin-like growth factor-1 (IGF-1) is a local activator of osteoblast activity. Studies have found that when IGFBP-4 binds to IGF-1, the biological activity of IGF-1 is inhibited. Studies have confirmed that the level of IGFBP-4 is regulated by synthesis and degradation. IGFBP-4 protease can specifically cleave IGFBP-4. PTH can induce and inhibit the activity of IGFBP-4 protease, but estrogen can eliminate the inhibition of IGFBP-4 protease activity triggered by PTH, thus eliminating the inhibition of osteogenic activity by PTH.
Reference
| Target | Cat. No. | Product Name | Expression System | Tag/Conjugate | Application | |
| PTH | DAG-IV03 | Recombinant Human PTH Protein | E.coli | N/A | Inquiry | |
| DAG-WT1941 | Recombinant Human PTH Protein [GST] | E. coli | GST | WB, ELISA | Inquiry | |
| DAG-WT1942 | Recombinant Human PTH Protein [hFc] | HEK293 cells | hFc | WB, ELISA | Inquiry | |
| PTH1R | DAG-WT1693 | Recombinant Human PTH1R VLP | HEK293 cells | N/A | N/A | Inquiry |
| PTH2R | DAG-WT1694 | Recombinant Human PTH2R VLP | HEK293 cells | N/A | N/A | Inquiry |
| Target | Cat. No. | Product Name | Size | Species Reactivity | Application | Detection Sample | |
| PTH | DEIA-BJ659 | Mouse I-PTH(intact PaRathormone) ELISA Kit | 96T | Mouse | Quantitative | Serum, plasma, tissue homogenates, other biological fluids | Inquiry |
| ABPR-ZB224 | Human Parathyroid Hormone/PTH Antibody Pair Set | 5 Plates, 15 Plates | Human | sELISA | Inquiry | ||
| DEIABL239D | PTH (1-84) Depletion Kit | 10 x 96 tests | N/A | Qualitative | Serum; Plasma. | Inquiry | |
| DEIABL239 | PTH (1-34)-Teriparatide ELISA Kit | 96T | Human | Quantitative | serum | Inquiry | |
| ABPR-0738 | Human PTH ELISA Matched Antibody Pair | ELISA | Inquiry | ||||
| DEIA1826B | Bovine Intact Parathormone ELISA Kit | 96T | Quantitative | serum, plasma, tissue homogenates and other biological fluids. | Inquiry | ||
| DEIA1836 | Human Intact-PTH ELISA Kit | 96T | Human | Quantitative | Human Serum | Inquiry | |
| PTHLH | DEIA-BJ695 | Human Parathormone 1-34 ELISA Kit | 96T | Human | Quantitative | serum, plasma | Inquiry |
| DEIA-BJ2246 | Rat Parathyroid Hormone Related Protein ELISA Kit | 96T | Quantitative | Serum, plasma, cell culture supernatants, body fluid and tissue homogenate | Inquiry | ||
| DEIA-BJ2556 | Mouse Parathyroid Hormone Related Protein ELISA Kit | 96T | Quantitative | Serum, plasma, cell culture supernatants, body fluid and tissue homogenate | Inquiry | ||
| DEIA2034 | PTH-RP ( 1-34 ) ( human, rat, mouse ) ELISA Kit | 96T | Human, Mouse, Rat | Quantitative | plasma | Inquiry |
| Target | Cat. No. | Product Name | Expression System | Tag/Conjugate | Application | |
| PTH | DAG-IV03 | Recombinant Human PTH Protein | E.coli | N/A | Inquiry | |
| DAG-WT1941 | Recombinant Human PTH Protein [GST] | E. coli | GST | WB, ELISA | Inquiry | |
| DAG-WT1942 | Recombinant Human PTH Protein [hFc] | HEK293 cells | hFc | WB, ELISA | Inquiry | |
| PTH1R | DAG-WT1693 | Recombinant Human PTH1R VLP | HEK293 cells | N/A | N/A | Inquiry |
| PTH2R | DAG-WT1694 | Recombinant Human PTH2R VLP | HEK293 cells | N/A | N/A | Inquiry |
| Target | Cat. No. | Product Name | Size | Species Reactivity | Application | Detection Sample | |
| PTH | DEIA-BJ659 | Mouse I-PTH(intact PaRathormone) ELISA Kit | 96T | Mouse | Quantitative | Serum, plasma, tissue homogenates, other biological fluids | Inquiry |
| ABPR-ZB224 | Human Parathyroid Hormone/PTH Antibody Pair Set | 5 Plates, 15 Plates | Human | sELISA | Inquiry | ||
| DEIABL239D | PTH (1-84) Depletion Kit | 10 x 96 tests | N/A | Qualitative | Serum; Plasma. | Inquiry | |
| DEIABL239 | PTH (1-34)-Teriparatide ELISA Kit | 96T | Human | Quantitative | serum | Inquiry | |
| ABPR-0738 | Human PTH ELISA Matched Antibody Pair | ELISA | Inquiry | ||||
| DEIA1826B | Bovine Intact Parathormone ELISA Kit | 96T | Quantitative | serum, plasma, tissue homogenates and other biological fluids. | Inquiry | ||
| DEIA1836 | Human Intact-PTH ELISA Kit | 96T | Human | Quantitative | Human Serum | Inquiry | |
| PTHLH | DEIA-BJ695 | Human Parathormone 1-34 ELISA Kit | 96T | Human | Quantitative | serum, plasma | Inquiry |
| DEIA-BJ2246 | Rat Parathyroid Hormone Related Protein ELISA Kit | 96T | Quantitative | Serum, plasma, cell culture supernatants, body fluid and tissue homogenate | Inquiry | ||
| DEIA-BJ2556 | Mouse Parathyroid Hormone Related Protein ELISA Kit | 96T | Quantitative | Serum, plasma, cell culture supernatants, body fluid and tissue homogenate | Inquiry | ||
| DEIA2034 | PTH-RP ( 1-34 ) ( human, rat, mouse ) ELISA Kit | 96T | Human, Mouse, Rat | Quantitative | plasma | Inquiry |
Loading ......
