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Frontiers in Endocrinology 2022
Topics: Humans; Calcium; Parathyroid Hormone; Hypocalcemia; Homeostasis
PubMed: 36644693
DOI: 10.3389/fendo.2022.1124762 -
International Journal of Molecular... Dec 2021Calciotropic hormones, parathyroid hormone (PTH) and calcitonin are involved in the regulation of bone mineral metabolism and maintenance of calcium and phosphate... (Review)
Review
Calciotropic hormones, parathyroid hormone (PTH) and calcitonin are involved in the regulation of bone mineral metabolism and maintenance of calcium and phosphate homeostasis in the body. Therefore, an understanding of environmental and genetic factors influencing PTH and calcitonin levels is crucial. Genetic factors are estimated to account for 60% of variations in PTH levels, while the genetic background of interindividual calcitonin variations has not yet been studied. In this review, we analyzed the literature discussing the influence of environmental factors (lifestyle factors and pollutants) on PTH and calcitonin levels. Among lifestyle factors, smoking, body mass index (BMI), diet, alcohol, and exercise were analyzed; among pollutants, heavy metals and chemicals were analyzed. Lifestyle factors that showed the clearest association with PTH levels were smoking, BMI, exercise, and micronutrients taken from the diet (vitamin D and calcium). Smoking, vitamin D, and calcium intake led to a decrease in PTH levels, while higher BMI and exercise led to an increase in PTH levels. In terms of pollutants, exposure to cadmium led to a decrease in PTH levels, while exposure to lead increased PTH levels. Several studies have investigated the effect of chemicals on PTH levels in humans. Compared to PTH studies, a smaller number of studies analyzed the influence of environmental factors on calcitonin levels, which gives great variability in results. Only a few studies have analyzed the influence of pollutants on calcitonin levels in humans. The lifestyle factor with the clearest relationship with calcitonin was smoking (smokers had increased calcitonin levels). Given the importance of PTH and calcitonin in maintaining calcium and phosphate homeostasis and bone mineral metabolism, additional studies on the influence of environmental factors that could affect PTH and calcitonin levels are crucial.
Topics: Animals; Calcitonin; Calcium; Homeostasis; Humans; Life Style; Parathyroid Hormone; Phosphates
PubMed: 35008468
DOI: 10.3390/ijms23010044 -
Frontiers in Endocrinology 2022Osteocytes are dendritic cells in the mineralized bone matrix that descend from osteoblasts. They play critical roles in controlling bone mass through the production of... (Review)
Review
Osteocytes are dendritic cells in the mineralized bone matrix that descend from osteoblasts. They play critical roles in controlling bone mass through the production of sclerostin, an inhibitor of bone formation, and receptor activator of nuclear factor κ B ligand, an inducer of osteoblastic bone resorption. Osteocytes also govern phosphate homeostasis through the production of fibroblast growth factor 23 (FGF23), which lowers serum phosphate levels by increasing renal phosphate excretion and reducing the synthesis of 1,25-dihydroxyvitamin D (1,25(OH)D), an active metabolite of vitamin D. The production of FGF23 in osteocytes is regulated by various local and systemic factors. (), (), and function as local negative regulators of FGF23 production in osteocytes, and their inactivation causes the overproduction of FGF23 and hypophosphatemia. Sclerostin has been suggested to regulate the production of FGF23, which may link the two functions of osteocytes, namely, the control of bone mass and regulation of phosphate homeostasis. Systemic regulators of FGF23 production include 1,25(OH)D, phosphate, parathyroid hormone, insulin, iron, and inflammation. Therefore, the regulation of FGF23 in osteocytes is complex and multifactorial. Recent mouse studies have suggested that decreases in serum phosphate levels from youth to adulthood are caused by growth-related increases in FGF23 production by osteocytes, which are associated with the down-regulation of and .
Topics: Animals; Bone Density; Fibroblast Growth Factors; Humans; Mice; Osteocytes; Parathyroid Hormone; Phosphates
PubMed: 35909535
DOI: 10.3389/fendo.2022.967774 -
Journal of Oral Biosciences Sep 2022The intermittent administration of parathyroid hormone (PTH) has been prescribed to osteoporotic patients due to its bone anabolic effects. In addition to its actions on... (Review)
Review
BACKGROUND
The intermittent administration of parathyroid hormone (PTH) has been prescribed to osteoporotic patients due to its bone anabolic effects. In addition to its actions on bone cells, PTH appears to affect bone-specific blood vessels. These blood vessels are derived from bone marrow sinusoids, which express EphB4, a hallmark of veinous vascular endothelial cells. Given the presence of osteo-vascular interactions, it is important to elucidate the effects of PTH on bone cells and blood vessels in murine models.
HIGHLIGHTS
PTH stimulates preosteoblastic proliferation and osteoblastic bone formation. The former appears to be directly affected by PTH, whereas the latter requires osteoclast-mediated coupling. The administration of PTH through high-frequency dosage schemes accelerates bone turnover featuring remodeling-based bone formation, whereas low-frequency schemes cause mainly remodeling-based and partly modeling-based bone formation. Normally, many blood vessels lack alpha smooth muscle actin (αSMA)-immunoreactive vascular muscle cells surrounding basement membranes, indicating them being capillaries. However, PTH administration increases the number of blood vessels surrounded by αSMA-positive cells. These αSMA-positive cells spread out of blood vessels and express alkaline phosphatase and c-kit, suggesting their potential to differentiate into osteogenic and vascular endothelial/perivascular cells. Unlike bone cells, αSMA-positive cells did not appear in the periphery of blood vessels in the kidney and liver, and the thickness of the tunica media did not change regardless of PTH administration.
CONCLUSION
Based on the results of the study and presence of osseous-vascular interactions, PTH appears to influence not only osteoblastic cells, but also blood vessels in bone.
Topics: Actins; Alkaline Phosphatase; Anabolic Agents; Animals; Endothelial Cells; Humans; Mice; Osteoblasts; Osteogenesis; Parathyroid Hormone
PubMed: 35977651
DOI: 10.1016/j.job.2022.08.002 -
Physiological Reports Apr 2022In the present study, we examined the systemic and direct effects of parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF-23) on duodenal, jejunal, and ileal...
In the present study, we examined the systemic and direct effects of parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF-23) on duodenal, jejunal, and ileal Mg absorption. The rats were injected with FGF-23 or PTH for 5 h before collecting the duodenum, jejunum, and ileum for Mg transport analysis in Ussing chambers. The duodenum, jejunum, and ileum were directly exposed to FGF-23, PTH, or FGF-23 plus PTH with or without cell signaling inhibitors for 150 min in Ussing chambers prior to performing the Mg transport study. The small intestinal tissues were also subjected to western blot analyses for FGF receptor (FGFR), PTH receptor (PTHR), Klotho, transient receptor potential melastatin 6 (TRPM6), and cyclin as well as the cystathionine β-synthase domain divalent metal cation transport mediator 4 (CNNM4) expression. The small intestine abundantly expressed FGFR and PTHR proteins, whereas, Klotho was not expressed in rat small intestine. Systemic PTH or FGF-23 injection significantly suppressed transcellular Mg transport in the duodenum and jejunum. Direct FGF-23-, PTH-, or FGF-23 plus PTH exposure also suppressed transcellular Mg absorption in the duodenum and jejunum. There was no additional inhibitory effect of PTH and FGF-23 on intestinal Mg absorption. The inhibitory effect of PTH, FGF-23, or FGF-23 plus PTH was abolished by Gö 6850. Systemic PTH- or FGF-23-injection significantly decreased membranous TRPM6 expression, but increased cytosolic CNNM4 expression in the duodenum, jejunum, and ileum. In the present study, we propose a novel magnesiotropic action of PTH and FGF-23 by modulating small intestinal Mg absorption.
Topics: Animals; Cation Transport Proteins; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Intestinal Absorption; Intestine, Small; Magnesium; Parathyroid Hormone; Rats
PubMed: 35385223
DOI: 10.14814/phy2.15247 -
Acta Physiologica (Oxford, England) May 2023Central to the maintenance of calcium homeostasis is the regulated reabsorption of calcium along the nephron. To this end, parathyroid hormone (PTH) is released from the... (Review)
Review
Central to the maintenance of calcium homeostasis is the regulated reabsorption of calcium along the nephron. To this end, parathyroid hormone (PTH) is released from the parathyroid gland in response to lowered plasma calcium levels. This hormone acts through the PTH 1 receptor along the nephron to increase urinary phosphate excretion and decrease urinary calcium excretion. In the proximal tubule, PTH inhibits phosphate reabsorption by reducing the abundance of sodium phosphate cotransporters in the apical membrane. PTH likely decreases calcium reabsorption from the proximal tubule, by reducing the reabsorption of sodium, an event necessary for the paracellular movement of calcium across this segment. In the thick ascending limb (TAL), PTH increases calcium permeability and may increase the electrical driving force thereby increasing calcium reabsorption in the TAL. Finally, in the distal convolution, PTH acts to increase transcellular calcium reabsorption by increasing the activity and abundance of the apically expressed calcium channel TRPV5.
Topics: Calcium; Parathyroid Hormone; Phosphates; Kidney Tubules; Kidney Tubules, Proximal
PubMed: 36894509
DOI: 10.1111/apha.13959 -
Frontiers in Endocrinology 2020The renin-angiotensin-aldosterone system (RAAS) is the regulatory system by which renin induces aldosterone production. Angiotensin II (Ang II) is the main effector... (Review)
Review
The renin-angiotensin-aldosterone system (RAAS) is the regulatory system by which renin induces aldosterone production. Angiotensin II (Ang II) is the main effector substance of the RAAS. The RAAS regulates blood pressure and electrolyte balance by controlling blood volume and peripheral resistance. Excessive activation of the RAAS is an important factor in the onset of cardiovascular disease and the deterioration of this disease. The most common RAAS abnormality is primary aldosteronism (PA). Parathyroid hormone (PTH) is a peptide secreted by the main cells of the parathyroid gland, which promotes elevated blood calcium (Ca) levels and decreased blood phosphorus (Pi) levels. Excessive secretion of PTH can cause primary hyperparathyroidism (PHPT). Parathyroidism is highly prevalent in postmenopausal women and is often associated with secondary osteoporosis. PA and PHPT are common endocrine system diseases. However, studies have shown a link between the RAAS and PTH, indicating a positive relationship between them. In this review, we explore the complex bidirectional relationship between the RAAS and PTH. We also point out possible future treatment options for related diseases based on this relationship.
Topics: Animals; Cardiovascular Diseases; Humans; Hyperparathyroidism; Parathyroid Hormone; Renin-Angiotensin System
PubMed: 32973674
DOI: 10.3389/fendo.2020.00539 -
The Surgeon : Journal of the Royal... Aug 2022National Institute of Clinical Excellence (NICE) recommend against routinely using Intra-Operative Parathyroid Hormone (IOPTH) for first-time parathyroid surgery due to...
BACKGROUND
National Institute of Clinical Excellence (NICE) recommend against routinely using Intra-Operative Parathyroid Hormone (IOPTH) for first-time parathyroid surgery due to its cost and minimal surgical benefit. The European Society of Endocrine Surgeons differ from this and recommends IOPTH with conflicting pre-operative or single imaging. NICE guidance acknowledged that this may change practice in larger centres. We devised a retrospective single-centre cohort study to analyse the impact of IOPTH on decision-making and cost-effectiveness.
METHODOLOGY
First-time parathyroidectomy procedures for primary hyperparathyroidism were assessed between 2017 and 2019. Ultrasound (US) and Sestamibi with parathyroid single-photon emission with computed tomography (SPECT-CT) were compared with IOPTH. The contribution of IOPTH to cure and cost effectiveness ratio was calculated.
RESULTS
114 cases were included, with IOPTH performed in all cases, SPECT-CT in 112 and US in 108 cases. A cure rate of 99.1% (113/114) was achieved. 11.4% (13/114) of the cure rate was influenced by IOPTH (P 0.01), instigating further exploration when its levels didn't decrease. This included 7.1% (4/56) in the concordant-imaging cohort. IOPTH accuracy (96.5%) was significantly superior (P = 0.03) to both US (80%) and SPECT-CT (81%). Comparing the total costs for IOPTH testing over 2 years (£39,721) with 13 potential re-operative procedures in its absence (£63,536), a positive cost-effectiveness ratio of £1832 per re-operative procedure averted was achieved.
CONCLUSION
Abandoning IOPTH in first-time parathyroid surgery is too ambitious when weighing the cost of re-operative surgery against cost savings obtained by using routine IOPTH to achieve an improved cure rate, even in concordant imaging.
Topics: Clinical Decision-Making; Cost-Benefit Analysis; Humans; Hyperparathyroidism, Primary; Minimally Invasive Surgical Procedures; Parathyroid Hormone; Parathyroidectomy; Practice Guidelines as Topic; Retrospective Studies; Single Photon Emission Computed Tomography Computed Tomography
PubMed: 34090811
DOI: 10.1016/j.surge.2021.04.008 -
The Journal of Steroid Biochemistry and... Jun 2022In vitro studies indicate that 25-hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) inhibits the synthesis of parathyroid hormone (PTH). The degree...
In vitro studies indicate that 25-hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) inhibits the synthesis of parathyroid hormone (PTH). The degree of PTH inhibition in humans by circulating 25(OH)D and 1,25(OH)2D may be different. Moreover, age and sex as well as confounding factors like calcium and phosphate may likewise affect the relationship between vitamin D and PTH in humans. However, this was not done so far in adequately powered studies. We investigated the relationship between 25(OH)D as well as 1,25(OH)2D and intact parathyroid hormone (iPTH) in 23,134 outpatients (age mean: 59.81 years) from the Berlin-Brandenburg area of Germany with normal serum creatinine considering confounding factors like age, sex, calcium and phosphate. 25(OH)D and iPTH were inversely correlated (r = -0.17, p < 0.0001). The inverse linear correlation was observed over the entire spectrum of 25(OH)D concentrations - from low 25(OH)D concentrations to very high 25(OH)D concentrations. Multiple linear regression analysis revealed that this correlation was independent of age, sex, creatinine, calcium and phosphate (unstandardized coefficients B: -0.16, p < 0.0001). However, 1,25(OH)2D was only positively associated with iPTH in women (r = 0.05, p = 0.033) and in the subgroup of patients with lower 25(OH)D (25(OH)D< 40 ng/ml) (r = 0.09, p < 0.0001), which was also presented in multiple linear regression analysis (unstandardized coefficients B: 0.20, p = 0.001). Circulating 1,25(OH)2D does not contribute substantially to the regulation of PTH in middle aged and vitamin D sufficient outpatients from the Berlin-Brandenburg area of Germany with normal kidney function. Presumably, serum 25(OH)D that is converted to 1,25(OH)2D after uptake in the parathyroid chief cells plays the critical role.
Topics: Calcifediol; Calcium; Calcium, Dietary; Female; Germany; Humans; Male; Middle Aged; Outpatients; Parathyroid Hormone; Phosphates; Vitamin D; Vitamins
PubMed: 35351538
DOI: 10.1016/j.jsbmb.2022.106101 -
Journal of Bone and Mineral Research :... Dec 2022
Topics: Humans; Hypoparathyroidism; Parathyroid Hormone
PubMed: 36375811
DOI: 10.1002/jbmr.4671