Calcitonin calcium homeostasis

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. 

The steroid hormone 1,25-dihydroxy vitamin D3 (calcitriol) slowly increases both intestinal calcium absorption and bone resorption, and is also stimulated through low calcium levels. In contrast, calcitonin rapidly inhibits osteoclast activity and thus decreases serum calcium levels. Calcitonin is secreted by the clear cells of the thyroid and inhibits osteoclast activity by increasing the intracellular cyclic AMP content via binding to a specific cell surface receptor, thus causing a contraction of the resorbing cell membrane. The biological relevance of calcitonin in human calcium homeostasis is not well established. 

A peptide hormone rapidly inhibiting osteoclast activity. The relevance of calcitonin in human calcium homeostasis is not well understood. Calcitonin has been used for the treatment of osteoporosis, although due to the availability of more potent drugs with less side effects, and the lack of clear data on the anti-fracture efficacy of calcitonin, its clinical use has been steadily declining. 

Vitamin D is really a small family of closely related molecnles that prevent the bone disease rickets in children and osteomalacia in adnlts. In both cases, inadeqnate mineralization of bone results in bone deformation and weakness. Calcinm, Ca +, homeostasis is one goal of vitamin D activity, a goal it shares with parathyroid hormone and calcitonin. Calcium is intimately involved in bone mineralization and distnrbances of calcium levels in the blood can resnlt in inadeqnate bone mineralization or excessive calcification of other tissues. 

CaR expression is greatest in the parathyroid glands, calcitonin-secreting C-cells of the thyroid gland, and kidney, but the CaR is also found in the two other key organs that participate in calcium homeostasis gut and bone (Brown and MacLeod, 2001). This review will focus on the structure and function of the CaR, its role in normal physiology and in various disorders of Ca -sensing, and the development of CaR-based therapeutics. 

PTH works with two other primary hormones— calcitonin and vitamin D—in regulating calcium homeostasis. These three hormones, as well as several other endocrine factors, are all involved in controlling calcium levels for various physiologic needs. How these hormones interact in controlling normal bone formation and resorption is of particular interest to rehabilitation specialists. Regulation of bone mineral homeostasis and the principal hormones involved in this process are presented in the following section. 

Some mechanisms contributing to bone mineral homeostasis. Calcium and phosphorus concentrations in the serum are controlled principally by two hormones, l,25(OH)2D3(D) and parathyroid hormone (PTH), through their action on absorption from the gut and from bone and on excretion in the urine. Both hormones increase input of calcium and phosphorus from bone into the serum vitamin D also increases absorption from the gut. Vitamin D decreases urinary excretion of both calcium and phosphorus, while PTH reduces calcium but increases phosphorus excretion. Calcitonin (CT) is a less critical hormone for calcium homeostasis, but in pharmacologic concentrations CT can reduce serum calcium and phosphorus by inhibiting bone resorption and stimulating their renal excretion. Feedback effects are not shown. 

Parathyroid hormone (PTH), vitamin D and calcitonin work in synchrony to regulate calcium homeostasis (not presented in tables). PTH is an 84 amino acid chain secreted by the parathyroid glands in response to low serum calcium. PTH induces bone resorption, which liberates calcium into the bloodstream. These actions are dependent on adequate serum concentrations of 1,25-dihydroxy cholecalciferol (a derivative of vitamin D). Bone resorption is counterregulated by calcitonin, which inhibits osteoclasts (the cells which degrade bone). 

Arnaud (7) has developed a butterfly model that provides a diagrammatic view of the complex interrelationships among the three hormones (parathyroid, calcitonin, and vitamin D) that control calcium homeostasis (serum concentrations of ionic calcium) and their target organs (bone, kidney, and intestine) (Fig. 35.1). The right side (B loops) of the butterfly model describes the processes that increase the serum calcium concentration in response to hypocalcemia the left side (A loops) depicts the events that occur in response to hypercalcemia. 

A polypeptide hormone, consisting of 32 amino acids, produced in the C cells of the thyroid gland. It is involved in calcium homeostasis, its main action being to decrease osteoclastic activity and therefore reduce bone resorption. Calcitonin also has a phosphaturic effect. It is secreted in response to high ionized calcium levels. High serum levels are found in patients with medullary carcinoma of the thyroid. It is usually measured by radioimmunoassay. 

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. 

The normal thyroid gland secretes sufficient amounts of the thyroid hormones—triiodothyronine (T3) and tetraiodothyronine (T4, thyroxine)—to normalize growth and development, body temperature, and energy levels. These hormones contain 59% and 65% (respectively) of iodine as an essential part of the molecule. Calcitonin, the second type of thyroid hormone, is important in the regulation of calcium metabolism and is discussed in Chapter 42 Agents That Affect Bone Mineral Homeostasis. 

Vitamin D, along with parathyroid hormone and calcitonin, plays a primary role in calcium and phosphorus homeostasis in the body. Intensive research efforts over the past several years have elucidated a role for vitamin D in many other physiological processes as well. The biological actions of this seco-steroid are mediated primarily through the action of its polar metabolite, 1,25-dihydroxy vitamin D3 (l,25(OH)2D3). There is emerging evidence that l,25(OH)2D3 has many more target tissues than those involved in its classical role in the control of mineral metabolism. In addition, some of the actions of l,25(OH)2D3 may be mediated by mechanisms other than the classical steroid-receptor interaction. In this chapter we will provide a brief overview of the multiple actions of vitamin D3 and the pleiotropic mechanisms by which these actions are accomplished. 

Q7 Calcium is present in both intracellular fluid (ICF) and ECF, but the concentration in the ECF is twice as high as that in the ICF. Calcium is found in both ionized and bound forms, and Ca2+ homeostasis is mainly controlled by parathyroid hormone, which increases absorption of calcium in the intestine and reabsorption in the nephron. Calcitonin also affects ECF calcium concentration by promoting renal excretion when there is an excess of calcium in the body. The normal kidney filters and reabsorbs most of the filtered calcium however, in renal disease this is reduced and blood calcium decreases. Calcium and phosphate imbalance can occur in patients with renal failure, leading to osteomalacia (defective mineralization of bone). Osteomalacia is mainly due to reduced production of 1,25-dihydroxycholecalciferol, an active form of vitamin D metabolized in the kidney. Deficiency of 1,25-dihydroxycholecalciferol reduces the absorption of calcium salts by the intestine. 

Dietary phosphate intake is usually 1.2 to 1.4 g (39 to 45 mmoi)/day, nearly twice the recommended intake, of which approximately 60% to 70% is absorbed, principally in the jejunum. As with calcium, both passive and active transport systems exist 1,25(OH)2D is the prmcipal regulator of the active transport of phosphate. PTH-stimulated synthesis of 1,25(0H)2D thus offsets the phosphaturic effect of PTH. The prevailing serum phosphate concentration also modulates renal 25(0H)D-la-hydroxylase. Phosphate depletion or hypophosphatemia stimulates formation of l,25(OH)2D by the kidneys. In general, at pharmacological concentrations, calcitonin has the opposite effect of PTH. It is unclear, however, if calcitonm has any physiological role in mineral homeostasis in adult humans. 

Four primary factors influencing calcium and phosphate homeostasis are diet, vitamin D and its metabolites, PTH, and calcitonin. Table 37-1 lists other hormones known to... 

Interaction of PTH, calcitonin, and serum concentrations of calcium and phosphate in calcium and phosphate homeostasis. [Modified and reproduced, with permission, from A. W. Norman, Vitamin D The Calcium Homeostatic Hormone. Academic Press, New York, 1979.]... 

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. ... 

Calcitonin is also involved in calcinm homeostasis by inhibiting bone resorption and by preventing excess increases in the serum calcium concentration throngh its monitoring of parathyroid hormone s actions (see Figure 75). 

---