Parathyroid hormone bone resorption, effect

Mechanism of Action An antibiotic that forms complexes with DNA, inhibiting DNA-directed RNA synthesis. May inhibit parathyroid hormone effect on osteoclasts and inhibit bone resorption. TherapeuticEffect Lowers serum calcium and phosphate levels. Blocks hypercalcemic action of vitamin Dand action of parathyroid hormone. Decreases serum calcium. 

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. 

Parathyroid hormone stimulates bone resorption by increasing the number and activity of osteoclasts. This demineralization process in the bone releases calcium and phosphate into the blood. Although the action of PTH on the bone appears to increase blood phosphate, its action on the kidney, which increases phosphate excretion in the urine, more than compensates for this increase and the net effect is a decrease in serum phosphate. 

The a ns wer is a. (Hardman, pp 1525-1528.) Pa r a thyroid ho r m o ne is synthesized by and released from the parathyroid gland increased synthesis of PTI1 is a response to low serum Ca concentrations. Resorption and mobilization of Ca and phosphate from bone are increased in response to elevated PTI1 concentrations. Replacement of body stores of Ca is enhanced by the capacity of PTH to promote increased absorption of Ca by the small intestine in concert with vitamin D, which is the primary factor that enhances intestinal Ca absorption. Parathyroid hormone also causes an increased renal tubular reabsorption of Ca and excretion of phosphate. As a consequence of these effects, the extracellular Ca concentration becomes elevated. 

Calcium-phosphorus balance is mediated through a complex interplay of hormones and their effects on bone, GI tract, kidney, and parathyroid gland. As kidney disease progresses, renal activation of vitamin D is impaired, which reduces gut absorption of calcium. Low blood calcium concentration stimulates secretion of parathyroid hormone (PTH). As renal function declines, serum calcium balance can be maintained only at the expense of increased bone resorption, ultimately resulting in renal osteodystrophy (ROD) (Fig. 76-7). 

A role for a collagenase, presumably fibroblast-type collagenase, in bone resorption has been indicated by studies employing the Searle A-carboxyl alkyl synthetic collagenase inhibitor CI-1 (compound (197) in Table 8.18) and its less potent stereoisomer CI-2 (compound (198) in Table 8.18) [207]. Cultured embryonic mouse calvaria treated with parathyroid hormone exhibit loss of calcium and show pronounced collagen resorption. CI-1 inhibited the collagen resorption in a dose-dependent manner at significantly lower concentrations than CI-2, but had only a small effect on calcium loss. This inhibitory effect was reversible and not due to inhibitor cytotoxicity. 

The polypeptide parathormone is released from the parathyroid glands when plasma Ca + level falls. It stimulates osteoclasts to increase bone resorption in the kidneys, it promotes calcium reabsorption, while phosphate excretion is enhanced. As blood phosphate concentration diminishes, the tendency of calcium to precipitate as bone mineral decreases. By stimulating the formation of vit D hormone, parathormone has an indirect effect on the enteral uptake of Ca + and phosphate. In parathormone deficiency, vitamin D can be used as a substitute that unlike parathormone, is effective orally. 

Estrogens have a number of important metabolic and cardiovascular effects. They seem to be partially responsible for maintenance of the normal structure and function of the skin and blood vessels in women. Estrogens also decrease the rate of resorption of bone by promoting the apoptosis of osteoclasts and by antagonizing the osteoclastogenic and pro-osteoclastic effects of parathyroid hormone and interleukin-... 

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. 

FIG. 15 Effect of lycopene on resorption of the calcium phosphate substrate coating of osteologic multitest slides in the presence of osteoclasts (Rao et al., 2003). (Lycopene I -Effect on osteoclasts Lycopene inhibits basal and parathyroid hormone-stimulated osteoclast formation and mineral resorption mediated by reactive oxygen species in ray bone marrow cultures. Reprint from Journal of Medicinal Food. 2003 6, pp. 69-78 by permission of Mary Ann Liebert, Inc., Publishers.)... 

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) 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-related protein receptor is a GPCR that acts via a Gas (and elevation of cAMP) or via Gaq (to activate PLC, increase IP3 and thence increase cytosolic Ca2+). PTH increases bone resorption and reabsorption of Ca2+ in the kidney with consequent elevation of blood Ca2+. Calcitonin, which binds to a GPCR that acts via a Gas to elevate C.AMP, has opposing effects to those of PTH. 

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. 

Physiologically, the response of bone to calcitriol is resorption of bone mineral and matrix protein. Both calcitriol and parathyroid hormone increase bone resorption in vivo and in bone organ culture, but have no effect on the activity of isolated osteoblasts. In addition to direct stimulation of the resorptive activity of osteoblasts, calcitriol increases osteoclastic activity. This is not because of a direct effect of calcitriol on osteoclasts, which lack calcitriol... 

Three effiects of parathyroid hormone The presence of parathyroid hormone in the plasma is required for the maintenance of I-hydroxylase activity in the kidney. The increase in PTH levels induces an increase in the activity of the hydroxylase, resulting in an increase in the production of l,25-(OH)D3 and an increase in the plasma levels of l,25-[OH)Di. In addition, PTH works in tandem with 1,25-(OH)2Dj in stimulating the osteodasts to dissolve bones and in increasing the efficiency of calcium resorption by the kidneys. Both PTH and l,25-(OH)2D3 are required for these latter two effects, i H is not required for the effect of the vitamin on the intestines. 

The osteoblast and osteoclast can be considered to be the basic multicellular units of bone. The osteoblast plays an important role in mediating local osteoclast activity through the release of chemical messengers. The principal factors responsible for stimulation of bone resorption, such as parathyroid hormone, interleukin-1 (Il-l), and IL-6, have minimal effects on osteoclasts, but osteoblasts have receptors for these substances. 

Effect of parathyroid hormone 1. increase bone resorption. 

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