Calcitonin

Literature References: Calcium regulating hormone secreted from the mammalian thyroid gland and in non-mammalian species from the ultimobranchial gland. Postulation of a plasma-calcium lowering substance: Copp et al., Endocrinology 70, 638 (1962). Recognition as a hormone: Hirsch et al., ibid. 73, 244 (1963); of thyroid origin: Foster et al., Nature 202, 1303 (1964). Over-all action is to oppose the bone and renal effects of parathyroid hormone, q.v.; inhibits bone resorption of Ca2+, with accompanying hypocalcemia and hypophosphatemia and decreased urinary Ca2+ concentrations. Also abolishes the osteolytic effect of toxic doses of vitamins A and D. Calcitonin is highly active biologically, e.g. 50 mg/min infused into a 100 g rat leads to a significant (1 mg/100 ml) decrease in the concn of the plasma calcium within 60 min (together with a corresponding fall in plasma phosphate). Activity is destroyed by trypsin, chymotrypsin, pepsin, polyphenol oxidase; also by hydrogen peroxide oxidation, photooxidation, and treatment with N-bromosuccinimide. Calcitonin structures are single polypeptide chains containing 32 amino acid residues. Structure of porcine: Neher et al., Helv. Chim. Acta 51, 917 (1968); Potts et al., Proc. Natl. Acad. Sci. USA 59, 1321 (1968); Bell et al., J. Am. Chem. Soc. 90, 2704 (1968); eidem, Biochemistry 9, 1665 (1970). Synthesis of porcine: Rittel et al., Helv. Chim. Acta 51, 924 (1968); Guttmann et al., ibid. 1155. Isoln of human calcitonin from non-pathological thyroid glands: Haymovits, Rosen, Endocrinology 81, 993 (1967); from medullary carcinoma of the thyroid: Neher et al., Nature 220, 984 (1968); Helv. Chim. Acta 51, 1738 (1968); Neher, Riniker, DE 1929957 (1970 to Ciba), C.A. 73, 28902b (1970). Structure of human: Neher et al., Helv. Chim. Acta 51, 1900 (1968). Synthesis of human: Sieber et al., ibid. 2057; J. Hirt et al., Rec. Trav. Chim. 98, 143 (1979). Biosynthetic studies: J. W. Jacobs et al., J. Biol. Chem. 254, 10600 (1979); S. G. Amara et al., ibid. 255, 2645 (1980). Amino acid sequence differs among mammalian species, salmon calcitonin showing a marked difference from that of the higher vertebrae as well as a more potent biological activity. Mechanism of action: E. M. Brown, G. D. Aurbach, Vitam. Horm. 38, 236 (1980). Anorectic activity in rats: W. J. Freed et al., Science 206, 850 (1979). Growth inhibition of human breast cancer cells in vitro: Y. Iwasaki et al., Biochem. Biophys. Res. Commun. 110, 235 (1983). Review of early literature: Munson, Hirsch, Clin. Orthop. 49, 209 (1966). Review of isoln, structure, synthesis: Behrens, Grinnan, Annu. Rev. Biochem. 38, 83 (1969); Potts et al., Vitam. Horm. 29, 41 (1971). Comprehensive review: Calcitonin, Proc. Symp. on Thyrocalcitonin and the C Cells, S. Taylor, Ed. (Springer-Verlag, New York, 1968); Foster et al., "Calcitonin" in Clinics in Endocrinology and Metabolism, I. MacIntyre, Ed. (W. B. Saunders, Philadelphia, 1972) pp 93-124. Review of pharmacology and therapeutic use: J. C. Stevenson, I. M. A. Evans, Drugs 21, 257-272 (1981).