Parathyroid hormone calcium regulation

A major regulator of bone metabolism and calcium homeostasis, parathyroid hormone (PTH) is stimulated through a decrease in plasma ionised calcium and increases plasma calcium by activating osteoclasts. PTH also increases renal tubular calcium re-absorption as well as intestinal calcium absorption. Synthetic PTH (1-34) has been successfully used for the treatment of osteoporosis, where it leads to substantial increases in bone density and a 60-70% reduction in vertebral fractures. 

It is now well established that l,25-(OH)2D3 is the active hormonal form of vitamin D3 [32], The production of l,25-(OH)2D3 in the kidney is regulated by dietary calcium and phosphate and also by changes in serum calcium and parathyroid hormone, which clearly highlight the hormonal nature of this compound. Functionally, the three classical actions of l,25-(OH)2D3 are to stimulate intestinal calcium and independently phosphate absorption, the mobilization of calcium from bone, and increase renal reabsorption of calcium. The focus of this review will be to explore the most recent concepts of vitamin D in regard to its metabolism and physiology, and with respect to the medicinal applications of vitamin D3 metabolites and analogues. 

Abnormalities in calcium or parathyroid hormone homeostasis may be a factor in depression. Significant fluctuations in calcitonin, a calcium-regulating hormone, and low plasma calcium levels during the menstrual cycle may play a part in the etiology of PMS. Calcium influx into brain cells is involved with the release of many neurotransmitters. Calcium supplementation (e.g., 1200-1600 mg/day of calcium carbonate in two divided doses) has been shown to reduce premenstrual symptoms such as anxiety, depression, irritability, mood swings, headache, fluid retention, and cramps. " " Calcium supplementation may help to prevent osteoporosis later in life, and it is a relatively safe and inexpensive treatment. ... 

These two hormones, together with the vitamin calcitriol, regulate calciumhomeostasis and thereby indirectly affect phosphate metabolism. Parathyroid hormone (parathormone PTH) is secreted by the parathyroid glands as a polypeptide of 84 amino acid residues, and its action is to increase plasma calcium via parathyroid hormone receptors in bone, kidney, and a few other tissues. PTH secretion is increased in response to hypocalcemia and hyperphosphatemia conversely, increased plasma calcium suppresses PTH secretion. The renal production of 1,25-dihydroxycholecalciferol is also... 

More than 99% of total body calcium is found in bone the remaining less than 1% is in the ECF and ICE Calcium plays a critical role in the transmission of nerve impulses, skeletal muscle contraction, myocardial contractions, maintenance of normal cellular permeability, and the formation of bones and teeth. There is a reciprocal relationship between the serum calcium concentration (normally 8.6 to 10.2 mg/dL [2.15 to 2.55 mmol/L]) and the serum phosphate concentration that is regulated by a complex interaction between parathyroid hormone, vitamin D, and calcitonin. About one-half of the serum calcium is bound to plasma proteins the other half is free ionized calcium. Given that the serum calcium has significant protein binding, the serum calcium concentration must be corrected in patients who have low albumin concentrations (the major serum protein). The most commonly used formula adds 0.8 mg/dL (0.2 mmol/L) of calcium for each gram of albumin deficiency as follows ... 

Around 99% of calcium is contained in the bones, whereas the other 1% resides in the extracellular fluid. Of this extracellular calcium, approximately 40% is bound to albumin, and the remainder is in the ionized, physiologically active form. Normal calcium levels are maintained by three primary factors parathyroid hormone, 1,25-dihydroxyvitamin D, and calcitonin. Parathyroid hormone increases renal tubular calcium resorption and promotes bone resorption. The active form of vitamin D, 1,25-dihydroxyvitamin D, regulates absorption of calcium from the GI tract. Calcitonin serves as an inhibitory factor by suppressing osteoclast activity and stimulating calcium deposition into the bones. 

Four small parathyroid glands are embedded on the posterior surface of the thyroid gland as it wraps around the trachea. Parathyroid hormone (PTH, parathormone) is the principal regulator of calcium metabolism. Its overall effects include ... 

Calcium is freely filtered along with other components of the plasma through the nephrons of the kidney. Most of this calcium is reabsorbed into the blood from the proximal tubule of the nephron. However, because the kidneys produce about 1801 of filtrate per day, the amount of calcium filtered is substantial. Therefore, the physiological regulation of even a small percentage of calcium reabsorption may have a significant effect on the amount of calcium in the blood. Parathyroid hormone acts on the Loop of Henle to increase the reabsorption of calcium from this segment of the tubule and... 

Human parathyroid hormone (hPTH) is an 84 amino acid polypeptide that functions as a primary regulator of calcium and phosphate metabolism in bones. It stimulates bone formation by osteoblasts, which display high-affinity cell surface receptors for the hormone. PTH also increases intestinal absorption of calcium. 

Parathyroid hormone (PTH) regulates calcium levels in blood and bone remodeling. The activation domain of that 84-amino acid polypeptide locates around the N-terminal (1-34 amino acids). Parathyroid hormone receptor is a typical G-protein coupled receptor, which is coupled to both adenyl cyclase/cAMP and PLCy/IP3/cytosolic Ca2+ intracellular signaling pathways. In order to identify the structural elements involved in the peptide hormone binding and signal initiation, Chorev et al. employed a photoaffinity scanning approach. The N-terminal amino acids were successively deleted or modified and the new N-terminus was replaced for photoreactive Bpa. The most active peptide ana-... 

The parathyroid hormone content of blood has not been studied sufficiently to yield any data with regard to variation. The functioning of the glands is so closely related to other factors which regulate calcium and phosphorus metabolism that it is impossible to assign differences in these areas to variation in parathyroid function. The variation of the calcium (and phosphorus) in the blood has been noted (p. 55), and this variation, of course, may be due in a substantial degree to differences in parathyroid functioning. 

Calcitonin is a polypeptide hormone which (along with parathyroid hormone and the vitamin D derivative, 1,25-dihydroxycholecalciferol) plays a central role in regulating serum ionized calcium (Ca +) and inorganic phosphate (P,) levels. The adult human body contains up to 2 kg of calcium, of which 98% is present in the skeleton (i.e. bone). Up to 85% of the 1kg of phosphorus present in the body is also found in the skeleton (the so-called mineral fraction of bone is largely composed of Ca3 (P04)2 which acts as a body reservoir for both calcium and phosphorus). Calcium concentrations in human serum approximate to O.lmg/ml and are regulated very tightly (serum phosphate levels are more variable). 

Three hormones serve as the principal regulators of calcium and phosphate homeostasis parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and the steroid vitamin D (Figure 42-2). Vitamin D is a prohormone rather than a true hormone, because it must be further metabolized to gain biologic activity. PTH stimulates the production of the active metabolite of vitamin D, l,25(OH)2D. l,25(OH)2D, on the other hand, suppresses the production of PTH. l,25(OH)2D stimulates the intestinal absorption of calcium and phosphate. l,25(OH)2D and PTH promote both bone formation and resorption in part by stimulating the proliferation and differentiation of osteoblasts and osteoclasts. Both... 

Cholecalciferol Regulate gene transcription via the vitamin D receptor Stimulate intestinal calcium absorption, bone resorption, renal calcium and phosphate reabsorption decrease parathyroid hormone (PTH) promote innate immunity inhibit adaptive immunity Osteoporosis, osteomalacia, renal failure, malabsorption Hypercalcemia, hypercalciuria the vitamin D preparations have much longer half-life than the metabolites and analogs... 

Regulation of 25-hydroxycholecalciferol 1-hydroxylase 1,25-diOH D3 is the most potent vitamin D metabolite. Its formation is tightly i regulated by the level of plasma phosphate and calcium ions (Figure 28.24). 25-Hydroxycholecalciferol1 -hydroxylase activity is I increased directly by low plasma phosphate or indirectly by bw I plasma calcium, which triggers the release of parathyroid hormone I... 

Parathyroid Hormones. T he influence of the parathyroid glands on the regulation of calcium concentrations in the hlood of mammals was first recognized hy MecCulhim and Vnegllin in I XW... 

The major location of calcium in the body is in the skeleton, which contains more than 90% of the body calcium as phosphate and carbonate. Bone resorption and formation keeps this calcium in dynamic equilibrium with ionized and complexed calcium in blood, cellular fluids and membranes. Homeostasis is mainly regulated by the parathyroid hormone and vitamin D which lead to increased blood calcium levels, and by a thyroid hormone, calcitonin, which controls the plasma calcium concentration J5 Increasing the concentration of calcitonin decreases the blood calcium level, hence injections of calcitonin are used to treat severe hyperalcaemia arising from hyperparathyroidism, vitamin D intoxication or the injection of too high a level of parathyroid extract. High levels of calcitonin also decrease resorption of calcium from bone. Hypocalcaemia stimulates parathyroid activity, leading to increased release of calcium from bone, reduction in urinary excretion of calcium and increased absorption of calcium from the intestine. Urinary excretion of phosphate is enhanced. 

Parathyroid hormone (PTH) is an 84-amino acid peptide secreted by the parathyroid glands, and is the principal regulator of extracellular calcium levels [44, 45]. The effects of PTH on extracellular calcium are mediated directly or indirectly through effects on bone, kidney, and intestine. A decrease in extracellular calcium causes an increase in PTH secretion. As a consequence, the rise in PTH levels causes increased bone resorption and the release of calcium from bone, decreased calcium excretion by the kidney, and increased intestinal calcium absorption. The therapeutic application of PTH has centered on the bone effects as an anabolic treatment for osteoporosis. PTH increases the activity of both osteoblasts (which form bone) and osteoclasts (which mediate bone resorption). The desirable anabolic effects of PTH on osteoblasts appear to be highly dependent on dose schedule and the duration of daily exposure. 

Parathyroid hormone (PTH) is an 84-amino acid polypeptide hormone that mediates bone remodeling and is an essential regulator of calcium homeostasis. Prolonged exposure to PTH changes the phenotype of the osteoblast from a cell involved in bone formation to one directing bone... 

Vitamin D that is taken up by the fiver is converted to 25-hydroxyvitamin D by a microsomal hydroxylase (Fig. 30-3). 25-Hydroxyvitamin D is the main circulating form of vitamin D in the serum and the best indicator of vitamin D status. Normal serum levels are 14-60 ng/mL (35-150 nmol/L). When serum calcium concentrations decline, 25-hydroxyvitamin D is converted to 1,25-dihydroxyvitmin D by la-hydroxylase, a mixed-function oxidase that is located in the inner mitochondrial membrane in kidney tissue and whose expression is regulated by parathyroid hormone (PTH). The main function of 1,25-dihydroxyvitamin D is to increase the intestinal absorption of dietary calcium and phosphorus. When serum concentrations of calcium and phosphorus are normal or when large doses of vitamin D are administered, 25-hydroxyvitamin D is metabolized to 24,25-dihydroxyvitamin D in the renal... 

Figure 30-5. Regulation of calcium homeostasis by the combined action of 1,25-dihydroxy vi ta m in D and parathyroid hormone (PTH). ECF, extracellular fluid.

The major function of the parathyroid hormone (PTH parathormone) is to regulate the concentration of extracellular calcium. PTH is heterogeneous and circulates as an intact polypeptide and as fragments. The major circulating biologically active peptide is intact PTH, which is rapidly cleared from the circulation (half-life less than 10 min). The N-terminal portion is responsible for its biologic activity. 

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