Parathyroid hormone calcium metabolism

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. 

The delicate balance maintained by these factors is altered in patients with cancer by two principal mechanisms tumor production of humoral factors that alter calcium metabolism (humoral hypercalcemia) and local osteolytic activity from bone metastases.27 Humoral hypercalcemia causes around 80% of all hypercalcemia cases and is mediated primarily by systemic secretion of parathyroid hormone-related protein... 

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 ... 

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. 

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. 

Enzyme induction properties Rifampin has enzyme induction properties that can enhance the metabolism of endogenous substrates including adrenal hormones, thyroid hormones, and vitamin D. Rifampin and isoniazid have been reported to alter vitamin D metabolism. In some cases, reduced levels of circulating 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D have been accompanied by reduced serum calcium and phosphate, and elevated parathyroid hormone. 

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... 

Conversion of 7-dehydrocholesterol to vitamin D3 and metabolism of D3 to l,25(OH)2D3 and 24,25(OH)2D3. Control of the latter step is exerted primarily at the level of the kidney, where low serum phosphorus, low serum calcium, and high parathyroid hormone favor the production of l,25(OH)2D3, whereas fibroblast growth factor 23 inhibits its production. The inset shows the... 

Vitamin D3 is a precursor of the hormone 1,25-dihy-droxyvitamin D3. Vitamin D3 is essential for normal calcium and phosphorus metabolism. It is formed from 7-dehydrocholesterol by ultraviolet photolysis in the skin. Insufficient exposure to sunlight and absence of vitamin D3 in the diet leads to rickets, a condition characterized by weak, malformed bones. Vitamin D3 is inactive, but it is converted into an active compound by two hydroxylation reactions that occur in different organs. The first hydroxylation occurs in the liver, which produces 25-hydroxyvita-min D3, abbreviated 25(OH)D3 the second hydroxylation occurs in the kidney and gives rise to the active product 1,25-dihydroxy vitamin D3 24,25 (OH)2D3 (fig. 24.13). The hydroxylation at position 1 that occurs in the kidney is stimulated by parathyroid hormone (PTH), which is secreted from the parathyroid gland in response to low circulating levels of calcium. In the presence of adequate calcium, 25(OH)D3 is converted into an inactive metabolite, 24,25 (OH)2D3. The active derivative of vitamin D3 is considered a hormone because it is transported from the kidneys to target cells, where it binds to nuclear receptors that are analogous to those of typical steroid hormones. l,25(OH)2D3 stimulates calcium transport by intestinal cells and increases calcium uptake by osteoblasts (precursors of bone cells). 

Mukai T. [Antagonism between parathyroid hormone and glucocorticoids in calcium and phosphorus metabolism. ]Nippon Naibunpi Gakkai Zasshi 1965 41(8) 950-9. 

Parathyroid Hormone. The role of the parathyroid gland and PTH in controlling calcium metabolism was previously discussed. A prolonged or continuous increase in the secretion of PTH increases blood calcium levels by several methods, including increased resorption of calcium from bone. High levels of PTH accelerate bone breakdown (catabolic effect) to mobilize calcium for other physiologic needs. 

FIGURE 61.5 Actions of vitamin D on calcium metabolism. PTH = parathyroid hormone. 

Endocrine and metabolic Blood tests Serum concentrations of pituitary horrmones (TSH, LH, FSH, ACTH, growth hormone, prolactin, vasopressin) serum concentrations of other hormones (insulin parathyroid hormone, glucagon, calcitonin, vitamin D) and serum electrolyte concentrations (sodium, potassium, calcium, magnesium)... 

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. 

Know the effects of parathyroid hormone, calcitonin, and vitamin D in controlling calcium and phosphate metabolism. Know what controls the levels of such hormones in the bloodstream. 

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... 

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. 

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. 

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. 

How does calcium work its wonders on blood pressure This gets a bit technical. The mineral reduces the concentration of parathyroid hormone in the blood that hormone regulates calcium metabolism. In turn, that might lower calcium concentrations in the body s cells and slow the calcium from entering the arteries. Calcium in the arteries affects the tone of the vessels, thus potentially leading to higher blood pressure as the arteries stiffen. 

A vitamin-deficient diet can result in lowered levels of plasma calcium however, the use of high-calcium diets during vitamin deficiency can result in the maintenance of normal plasma calcium levels. The requirement for the vitamin may be overridden, providing that the diet contains high levels of calcium. The physiologically important form of vitamin D, 1,25 dihydroxyvitamin Dj, is a hormone. Another hormone, parathyroid hormone (I TH), is used in the control of vitamin D metabolism and calcium levels, as detailed in the following sechon. 

The second most common adverse effect of foscarnet is symptomatic hjrpocalcemia, which may be responsible for the cardiac dysrhythmias and seizures that occur after acute overdose or excessively rapid infusion of foscarnet. Foscarnet stimulates the release of parathyroid hormone, which raised concerns about long-term administration (8). However, in a study of seven patients receiving a 14-day foscarnet induction regimen, there were no changes in calcium or phosphate metabolism (9). 

In lithium treated subjects, there is no evidence of reduced bone mass at any of the measured sites in relation to that of control subjects. The mechanism responsible for the maintenance of bone mass despite biochemical evidence of hyperparathyroidism is not clear [45]. We suspect that it is due to renal calcium retention. Indeed, in dogs lithium administration for only 3 days causes a striking decrease in urinary calcium excretion which is independent of the presence of parathyroid hormone and occurs despite the concurrent development of metabolic acidosis [Batlle D, Arruda J, and Kurtzman NA 1981 unpublished observations]. 

The physiological role of vitamin D is to maintain calcium homeostasis. Phosphate metabolism is also affected. Vitamin D accomplishes its role by enhancing the absorption of calcium and phosphate from tte small intestines, promoting their mobilization from bone, and decreasing their excretion by the kidney. Also involved are parathyroid hormone and edeitonin. 

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