Parathyroid Hormone and Calcitonin

The novel method of isolation of peptide amides [129] yielded an additional gastrointestinal peptide with biological activities. Galanine, H-Gly-Trp-Thr-Leu-Asn-Ser-Ala-Gly-Tyr-Leu-Leu-Gly-Pro-His-Ala-Ile-Asp-Asn-His-Arg-Ser Phe-HiS Asp Lys-Tyr-Gly-Leu-Ala-NH2 raises the blood sugar level and contracts the isolated rat ileum. Synthesis of the (porcine) peptide followed [133] its isolation and sequence determination within a short time. 

The remarkable progress in the chemistry and physiology of the gastrointestinal hormones in the last decades is due to the unrelenting efforts of Professors J. Erik Jorpes and Viktor Mutt in the Karolinska Institute, Stockholm, Sweden. 

The vital regulation of the level of calcium ions in the blood is under the control of two peptide hormones. The parathyroid hormone raises the concentration of blood calcium by mobilizing calcium uptake from the bones, while the thyroid hormone calcitonin directs the flow of calcium ions in the opposite direction. Thus a constant calcium ion level can be maintained in the blood. Both hormones stimulated extensive research but here we can discuss only some later developments that brought clarity into the picture. 

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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. 

Three additional recombinant hormones have recently gained marketing approval thyroid-stimulating hormone, parathyroid hormone and calcitonin. 

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. 

The Ca -selective hormones calcitriol, parathyroid hormone, and calcitonin influence this interaction in the bone cells. Parathyroid hormone promotes Ca "" release by promoting the release of cytokines by osteoblasts. In turn, the cytokines stimulate the development of mature osteoclasts from precursor cells (bottom). Calcitonin inhibits this process. At the same time, it promotes the development of osteoblasts (top). Osteoporosis, which mainly occurs in women following the menopause, is based (at least in part) on a reduc-... 

Calcium is present in three forms e.g., as free calcium ion, bound to plasma protein albumin and in diffusable complexes. The endocrine system, through parathyroid hormone and calcitonin, helps in keeping the concentration of ionized plasma calcium in normal level. Decrease in plasma levels of ionized calcium leads to increased parathyroid hormone secretion. Parathyroid hormone tends to increase plasma calcium level by increasing bone resorption, increasing intestinal absorption and increasing reabsorption of calcium in kidney. Vitamin D acts by stimulating... 

Nagata, N., Kimura, N., Sasaki, M., Nakane, K., Tanaka, Y. Localization of cell groups sensitive to parathyroid hormone and calcitonin in rat skeletal tissue. Biochim. Biophys. Acta 421, 218(1976)... 

The calcium taken up by living systems will be found mainly as extracellular deposits or structures, with a small amount present in intracellular stores, together with some in various extracellular fluids. The calcium in fluids will be bound to protein or will be free in solution, with a few percent bound to small molecules or anions. The calcium in solution will exchange with the calcium in structures such as bone and teeth, due to the activity of hormones such as l,25-(OH)2D3, parathyroid hormone and calcitonin,455 which are responsible for the remodelling and repair of bone. 

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. 

Sethi R, Kukreja SC, Bowser EN, Hargis GK, Henderson WJ, Williams GA, Effect of meal on serum parathyroid hormone and calcitonin possible role... 

Know about regulation of serum calcium including the roles of parathyroid hormone and calcitonin. 

Nineteen additional recombinant hormones have been approved thus far. These include a number of recombinant versions of human growth hormone (hGH), various gonadotropins, glucagon, parathyroid hormone and calcitonin (Table 4). Amongst these Somaverf is notable in that it is a recombinant PEGylated analog of hGH. It... 

Thyroid hormone also has an influence on growth by potentiating the effects of growth hormone and on skeletal development by affecting the action of parathyroid hormone and calcitonin. 

In a second study, the effect of oxcarbazepine monotherapy for 18 months on bone turnover was longitudinally explored in 34 newly diagnosed prepubertal and pubertal children [227 ]. The serum concentrations of 25-hydroxycolecalciferol were significantly reduced by oxcarbazepine, while osteocalcin and gamma-glutamyl transferase activity were significantly increased compared with baseline values. Phosphorus, parathyroid hormone, and calcitonin concentrations and alkaline phosphatase activity increased non-significantly. In three patients who had... 

The remaining 1 % of the calcium-about 10 g in an adult— is widely distributed in the soft tissues and the extracellular fluids. The vital role of this small amount of calcium is reflected in the precision with which plasma calcium is regulated, a narrow range of 9 to 11 g that is controlled by the parathyroid hormone and calcitonin. 

Phosphorus is closely associated with calcium in human nutrition— to the extent that a deficiency or an overabundance of one may very likely interfere with the proper utilization of the other. Also, both calcium and phosphorus occur in the same major food source—milk both function in the major task of building bones and teeth both are related to vitamin D in the absorption process both are regulated metabolically by the parathyroid hormone and calcitonin both exist in... 

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