Parathyroid

Blood Calcium Ion Level. In normal adults, the blood Ca " level is estabhshed by an equiUbrium between blood Ca " and the more soluble intercrystalline calcium salts of the bone. Additionally, a subtle and intricate feedback mechanism responsive to the Ca " concentration of the blood that involves the less soluble crystalline hydroxyapatite comes into play. The thyroid and parathyroid glands, the fiver, kidney, and intestine also participate in Ca " control. The salient features of this mechanism are summarized in Figure 2 (29—31). 

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). 

Magnesium ion is essential for normal Ca " and K" metaboHsm. In acute experimental magnesium deficiency in humans, hypocalcemia occurs despite adequate calcium intake and absorption and despite normal renal and parathyroid functions. Negative K" balance is also observed. AH biochemical and clinical abnormaHties disappear upon restoration of adequate amounts of magnesium to the diet (64). 

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. 

Three hormones regulate turnover of calcium in the body (22). 1,25-Dihydroxycholecalciferol is a steroid derivative made by the combined action of the skin, Hver, and kidneys, or furnished by dietary factors with vitamin D activity. The apparent action of this compound is to promote the transcription of genes for proteins that faciUtate transport of calcium and phosphate ions through the plasma membrane. Parathormone (PTH) is a polypeptide hormone secreted by the parathyroid gland, in response to a fall in extracellular Ca(Il). It acts on bones and kidneys in concert with 1,25-dihydroxycholecalciferol to stimulate resorption of bone and reabsorption of calcium from the glomerular filtrate. Calcitonin, the third hormone, is a polypeptide secreted by the thyroid gland in response to a rise in blood Ca(Il) concentration. Its production leads to an increase in bone deposition, increased loss of calcium and phosphate in the urine, and inhibition of the synthesis of 1,25-dihydroxycholecalciferol. 

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

A form of hypoparathyroidism (hypofimction of the parathyroid glands) caused by the presence of activating mutations in the CaR, usually in the heterozygous state. 

PTH is the most important regulator of bone remodelling and calcium homeostasis. PTH is an 84-amino acid polypeptide and is secreted by the parathyroid glands in response to reductions in blood levels of ionised calcium. The primary physiological effect of PTH is to increase serum calcium. To this aim, PTH acts on the kidney to decrease urine calcium, increase mine phosphate, and increase the conversion of 25-OH-vitamin D to l,25-(OH)2-vitamin D. PTH acts on bone acutely to increase bone resorption and thus release skeletal calcium into the circulation. However, due to the coupling of bone resorption and bone formation, the longer-term effect of increased PTH secretion is to increase both bone resorption and bone formation. 

The parathyroid glands in FHH are reset to maintain a higher than normal serum calcium concentration owing to impaired suppression of PTH release in the face of hypercalcemia (e.g., resistance to CaQ+) (Fig. 2). Similarly the kidneys show a reduced calciuric response to hypercalcemia, which contributes to the hypercalcemia by promoting inappropriately reabsorption of calcium. Mouse models of FHH and NSHPT result from targeted inactivation of one or both CaR alleles, respectively [1,3]. These animals have provided valuable insights into the alterations in tissue function resulting from loss of the receptor. 

A common cause of PTH-dependent hypercalcemia results from benign, or occasionally malignant, enlargement of one or more parathyroid glands, a condition known as primary hyperparathyroidism (PHPT). Although many patients with PHPT present in an asymptomatic state that does not require medical intervention, some are afflicted with excess bone loss, kidney stones, or other complications. If patients are... 

Some patients with reduced or absent parathyroid function, e.g., primary hypoparathyroidism, harbor anti-CaR antibodies (Fig. 2) [4]. In two patients, the antibodies were shown to activate the CaR as assessed by stimulation of MAPK and PLC. Tims, analogous to activating mutations of the CaR, anti-CaR antibodies can increase the sensitivity of the receptor to CaQ+, thereby resetting parathyroid and kidney to maintain hypocalcemia. 

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

In the periphery, dopamine receptor levels are generally lower than those observed in brain, particularly in comparison to striatal dopamine receptor levels. Due to these low levels, knowledge of receptor distribution in the periphery is not yet comprehensive. Nevertheless, Dl-like receptors have been reported in the parathyroid gland and in the tubular cells of the kidney. D2-like dopamine receptors have also been observed in the kidney. In addition, dopamine D2 and D4 receptors have been found in the adrenal cortex, where they modulate aldosterone secretion. The... 

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. 

A form of PTH-dependent hypercalcemia caused by enlargement and hyperfunction of one or more parathyroid glands. 

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... 

Other Inflammatory Muscle Disorders Endocrine Myopathies Thyroid Disorders Adrenal Disorders Pituitary Disorders Parathyroid Disorders Pancreatic Disorders Drug-Induced and Toxic Myopathies Management of Muscle Disease... 

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