Hormones parathyroid

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. 

Teriparatide, the N-terminal 34-mer of full-length PTH, is currently approved for the treatment of men or post-menopausal women who are at a high risk for fracture. Teriparatide is the only approved anabolic treatment for osteoporosis other drugs for osteoporosis primarily affect bone resorption [46, 47]. Teriparatide 

2 Parathyroid Hormone Parathyroid hormone raises plasma calcium by direct effects on bone resorption and renal reabsorption of calcium, and indirectly by regulating the metabolism of vitamin D. It is a peptide and acts via cell surface G-protein receptors linked to adenylate cyclase. The parathyroid glands have G-protein cell surface calcium receptors linked to phospholipase G, and parathyroid hormone is secreted in response to hypocalcemia. Magnesium is required for secretion of the hormone, which may explain the development of hypocalcemia in premature infants who are magnesium deficient. 

In the kidneys, parathyroid hormone increases 1 -hydroxylation of calcidiol and reduces 24-hydroxylation. This is not the result of de novo enzyme synthesis, but an effect on the activity of the preformed enzymes, mediated by cAMP-dependent protein kinases. In turn, calcitriol has a direct role in the control of parathyroid hormone, acting to repress expression of the gene. In chronic renal failure, there is reduced synthesis of calcitriol, leading to the development of secondary hyperparathyroidism that results in excess mobilization of bone mineral, hypercalcemia, hypercalciuria, hyperphosphaturia, and the development of calcium phosphate renal stones. 

PTH is a polypeptide hormone that is synthesized within the cells of the parathyroid glands. The primary factor controlling the release of PTH is the amount of calcium in the bloodstream.36 A calciumsensing receptor is located on the outer surface of the parathyroid cell membrane, and this receptor monitors plasma calcium levels.11,88 A decrease in plasma calcium activates this receptor and causes increased release of PTH. As blood calcium levels increase, the receptor is inhibited, and PTH release is reduced. 

Finally, PTH helps increase the absorption of calcium from the gastrointestinal tract. This effect appears to be caused by the interaction between PTH and vitamin D metabolism. PTH increases the conversion of vitamin D to 1,25-dihydroxycholecalciferol (calcitriol).36 Calcitriol directly stimulates calcium absorption from the intestine. 

Consequently, PTH is crucial to maintaining adequate levels of calcium in the body. In addition, 

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Fig. 2. Homeostatic control of blood Ca " level where PTH is parathyroid hormone [9002-64-6], CC, cholecalciferol, ie, vitamin D HCC, hydroxycholecalciferol DHCC, dihydroxycholecalciferol CaBP, calcium-binding protein NAD PH, protonated nicotinarnide-adenine dinucleotide...

Factors controlling calcium homeostasis are calcitonin, parathyroid hormone(PTH), and a vitamin D metabolite. Calcitonin, a polypeptide of 32 amino acid residues, mol wt - SGOO, is synthesized by the thyroid gland. Release is stimulated by small increases in blood Ca " concentration. The sites of action of calcitonin are the bones and kidneys. Calcitonin increases bone calcification, thereby inhibiting resorption. In the kidney, it inhibits Ca " reabsorption and increases Ca " excretion in urine. Calcitonin operates via a cyclic adenosine monophosphate (cAMP) mechanism. 

Parathyroid hormone, a polypeptide of 83 amino acid residues, mol wt 9500, is produced by the parathyroid glands. Release of PTH is activated by a decrease of blood Ca " to below normal levels. PTH increases blood Ca " concentration by increasing resorption of bone, renal reabsorption of calcium, and absorption of calcium from the intestine. A cAMP mechanism is also involved in the action of PTH. Parathyroid hormone induces formation of 1-hydroxylase in the kidney, requited in formation of the active metabolite of vitamin D (see Vitamins, vitamin d). 

Pseudohypoparathyroidism is characterized by end-organ resistance to parathyroid hormone (98,108). This disease takes various forms, including Albright s hereditary osteodystrophy, which has unusual physical features and a generalized resistance to G-protein-linked hormones that function through cAMP as a second messenger. This defect is associated with a deficiency in the levels of the a-subunit of (109). Because this defect may be generalized, such patients also have olfactory dysfunction (110). 

Several years ago, it was discovered that the thyroid gland was also the source of a hypocalcemic hormone having effects in general opposition to those of the parathyroid hormone. This hormone is produced in mammals by the parafollicular C-ceUs and in other vertebrates by the ultimobrachial bodies (45). Originally called thyrocalcitonin, it is now referred to as calcitonin (CT). 

Although it is being found that vitamin D metaboUtes play a role ia many different biological functions, metaboHsm primarily occurs to maintain the calcium homeostasis of the body. When calcium semm levels fall below the normal range, 1 a,25-dihydroxy-vitainin is made when calcium levels are at or above this level, 24,25-dihydroxycholecalciferol is made, and 1 a-hydroxylase activity is discontiaued. The calcium homeostasis mechanism iavolves a hypocalcemic stimulus, which iaduces the secretion of parathyroid hormone. This causes phosphate diuresis ia the kidney, which stimulates the 1 a-hydroxylase activity and causes the hydroxylation of 25-hydroxy-vitamin D to 1 a,25-dihydroxycholecalciferol. Parathyroid hormone and 1,25-dihydroxycholecalciferol act at the bone site cooperatively to stimulate calcium mobilization from the bone (see Hormones). Calcium blood levels are also iafluenced by the effects of the metaboUte on intestinal absorption and renal resorption. 

DHD = 24(R),25-dihydroxyvitamiQD2 250H = 25-hydroxyvitamia D PTH = parathyroid hormone CT = calcitonin F. = inorganic phosphoms. 

The overall effect in most animals is to stimulate intestinal absorption of calcium with a concomitant increase in semm calcium and a reduction in parathyroid hormone (PTH). Modest hypercalcemia allows the glomerular filtration rate to remain stable and hypercalciuria to occur because of increased filtered load of calcium and reduction of tubular resorption of calcium with reduced PTH. However, with further increases in semm calcium, the glomerular filtration rate decreases, resulting in an even more rapid increase in semm calcium and the subsequent fall in urinary calcium. 

Parathyroid hormone Glucoco r ticoid(s) Mineralo co r ticoid(s)... 

Nemeth EF (2002) Pharmacological regulation of parathyroid hormone secretion. Curr Pharm Des 8 2077-2087... 

Systemic regulators of osteoblast, osteocyte and osteoclast functions, and therefore of bone metabolism. The major bone-seeking hormones are parathyroid hormone (PIH), 1,25-dihydroxy vitamin D3 (calcitriol) and the various ex hormones. 

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. 

Most GPCRs interact with and activate more than one G-protein subfamily, e.g., with Gs plus Gq/n (histamine H2, parathyroid hormone and calcitonin recqrtors), Gs plus G (luteinising hormone receptor, 32-adrenoceptor) or Gq/11 plus G12/13 (thromboxane A2, angiotensin ATb endothelin ETA receptors). Some receptors show even broader G-protein coupling, e.g., to Gi, Gq/n plus Gi n ( protease-activated receptors, lysophosphatidate and sphingosine-1-phosphate receptors) or even to all four G-protein subfamilies (thyrotropin receptor). This multiple coupling results in multiple signaling via different pathways and in a concerted reaction of the cell to the stimulus. 

Parasympathetic Nervous System Parasympatholytics Parasympathomimetics Parathyroid Hormone Paraventricular Nucleus Parkin... 

Molecules released by exocytosis fall into three categories (1) They can attach to the cell surface and become peripheral proteins, eg, antigens. (2) They can become part of the extracellular matrix, eg, collagen and glycosaminoglycans. (3) They can enter extracellular fluid and signal other cells. Insulin, parathyroid hormone, and the catecholamines are all packaged in gran-... 

Luteinizing hormone Melanocyte-stimulating hormone Parathyroid hormone Somatostatin... 

Parathyroid Hormone (PTH) Is Secreted as an 84-Amino-Acid Peptide... 

Figure 42-13. Structure of bovine preproparathyroid hormone. Arrows indicate sites cieaved by processing enzymes in the parathyroid giand (1-5) and in the iiver after secretion of the hormone (4-5). The bioiogicaiiy active region of the moiecuie is fianked by sequence not required for activity on target receptors. (Slightly modified and reproduced, with permission, from Habener JF Recent advances in parathyroid hormone research. Clin Biochem 1981 14 223.)...

Parathyroid hormone also exists in storage vesicles. As much as 80-90% of the proPTH synthesized is degraded before it enters this final storage compartment, especially when Ca + levels are high in the parathyroid cell (see above). PTH is secreted when Ca is low in the parathyroid cells, which contain a several-hour supply of the hormone. 

Many factors are involved in the regulation of bone metabolism, only a few of which will be mentioned here. Some stimulate osteoblasts (eg, parathytoid hormone and 1,25-dihydroxycholecalciferol) and others inhibit them (eg, corticosteroids). Parathyroid hormone and 1,25-dihydroxycholecalciferol also stimulate osteoclasts, whereas calcitonin and estrogens inhibit them. 

Brewer, H. B. Falrwell, T. Ronan, R. Sizemore, 6. W. Arnaud, C. D. "Human Parathyroid Hormone Amlno-Acld Sequence of the Amlno-Termlnal Residues 1-34". Proc. Natl. Acad. Sci. IBA, (1972), 69, 3585-3588. 

J. T. Jr. "The Amlno-Acld Sequence of the Amlno-Termlnal 37 Residues of Human Parathyroid Hormone". Proc. Natl. 

Arnaud, C. D. Brewer, H. B. Jr. "Parathyroid Hormone Structure and Immunoheterogenelty" In Methods In Radioimmunoassay, Toxicology and Related Areas". Progress In Analytical Chemistry, pp. 45-75, Vol. 8, Simmons, I. L. and Ewing, 6. W., Editors, Plenum Press, New York and London, 1974. 

Silverman, R. Yalow, R. S. "Heterogeneity of Parathyroid Hormone Clinical and Physiologic Implications". J. Clin. Invest. (1973), 52, 1958-1971. 

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