Thyrocalcitonin

Hormones have recently been discovered that are likely to act on bone by either preventing resorption or facilitating deposition of calcium [29-31]. One of these hormones was found in the parathyroid gland (calcitonin), the other, in the thyroid gland (thyrocalcitonin). Thyro-calcitonin, which has been purified from pig thyroids, is a polypetide hormone with a molecular weight of 3,000 and composed of 32 amino acids (see Fig. 5-13). The intact sequence is indispensable for activity. The amino terminal segment of the molecule contains an intrachain disulfide bridge. 

The amino acid sequences of porcine, bovine, human, and salmon calcitonin are known. That of porcine calcitonin is shown in Fig. 5-13. Studies relating structure and activity have begun, but it is too early for any definite conclusion. Of the 32 amino acids, 18 in the human calcitonin sequence differ from those in the porcine hormone, and salmon calcitonin is more active in mammals than all known mammalian calcitonins. Moreover, the effect of salmon calcitonin is much longer than that of mammalian calcitonin. 

The homologies between all forms of calcitonins involve the amino terminal segment of the molecule (1-9).  

A proline terminal occupies the carboxy terminal position in all cases. Thus the variations affect the amino acids occupying positions 10-30 in the sequence. Such findings suggest that the amino terminal segment is directly linked to activity, and that the sequence between amino acid positions 10 and 30 regulates the level and duration of activity. In all cases (except one), all shifts in the sequence involve a single-base mutation in the triplet codon. 

The infusion of calcitonin to rats induces increased calcium deposition in the bone and hypocalcemia. Thus, the hormone has properties antagonistic to those of parathormone. Fluorescent antibody techniques have demonstrated that the hormone is secreted by the C cells of the thyroid gland. A light cell hyperplasia outside the follicular walls of the thyroid has been observed in mice with hereditary hypocalcemia. 

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The main role of the human thyroid gland is production of thyroid hormones (iodinated amino acids), essential for adequate growth, development, and energy metaboHsm (1 6). Thyroid underfunction is an occurrence that can be treated successfully with thyroid preparations. In addition, the thyroid secretes calcitonin (also known as thyrocalcitonin), a polypeptide that lowers excessively high calcium blood levels. Thyroid hyperfunction, another important clinical entity, can be corrected by treatment with a variety of substances known as antithyroid dmgs. 

Several years ago, it was discovered that the thyroid gland was also the source of a hypocalcemic hormone having effects in general opposition to those of the parathyroid hormone. This hormone is produced in mammals by the parafollicular C-ceUs and in other vertebrates by the ultimobrachial bodies (45). Originally called thyrocalcitonin, it is now referred to as calcitonin (CT). 

Chemical Name Complex hormone of molecular weight about 4,500 Common Name Thyrocalcitonin... 

PG Pietta, PF Cavallo, K Takahashi, GR Marshall. Preparation and use of benzhydrylamine polymers in peptide synthesis. II. Syntheses of thyrotropin releasing hormone, thyrocalcitonin 26-32, and eledoisin. J Org Chem 39, 44, 1974. 

Calcitonin and Thyrocalcitonin David Webster and Samuel C. Frazer... 

Steady-state fluorescence polarization studies have been carried out with a number of peptides, including model peptides, ACTH, glucagon, melittin, and thyrocalcitonin. This work has been reviewed 5 and will not be discussed in the present article. More recently, interesting information on the rotational behavior and structural flexibility of various peptides has been obtained from fluorescence anisotropy decay measurements. 

In 46 patients with Paget s disease given synthetic salmon thyrocalcitonin 80 IU/day for 3 months, there were hot flushes in 35% and nausea in 24% in only one case was it necessary to stop treatment because of intractable diarrhea (16). 

Bouvet JP. Traitement de la maladie de Paget par la thyr-ocalcitonine de saumon. Etude cooperative en double insu. [Treatment of Paget s disease with salmon thyrocalcitonin. Cooperative double-blind study.] Nouv Presse Med 1976 6(17) 1447-50. 

Thyrer thyrotrophin-releasing hormone, thyreotrophic hormone thyrotrophin. thyrocalcitonin calcitonin. a thyrocalcitonin calcitonin (pork), thyroglobulin [inn, usan] is obtained from thyroid glands of Sus scrota (hog), and contains >0.7% total iodine. It acts as a THYROID HORMONE, and was formerly used in the treatment of hypothyroidism. 

The extraction procedures used for thyrocalcitonin preparation have been applied to many other tissues, in a search for further hypocalcemic agents. Hirsch et al. (H4) were unable to demonstrate hypocalcemic activity in extracts of ox thymus, rat pituitary, or rat parathyroid. Rat liver, kidney, and salivary gland likewise yielded inactive extracts on assay in the rat. Gudmundsson et al. (G4) found no significant activity in pig liver, bovine parathyroid, or kidney. Extracts of dog lung, kidney, myocardium, skeletal muscle, spleen, brain, liver, and pancreas, when prepared by methods that yield potent extracts from the thyroid, failed to demonstrate hypocalcemic activity (CIO). Extracts of sheep liver and of gluteal muscle showed no activity in the sheep, and high-calcium perfusion of the thymus, isolated from parathyroid tissue, produced no... 

It seems to be fully established that the thyroid gland in many animal species contains a substance or substances (thyrocalcitonin) able to lower the plasma calcium concentration, and secreted in response to the passage of hypercalcemic blood through the gland. Potent extracts can be prepared, and are active when injected or infused into normal and parathyroidectomized animals. This substance is quite distinct from thyroid hormone. 

Factors Affecting the Rate of Secretion of Thyrocalcitonin 3.1. Plasma Calcium Level... 

The effects of plasma constituents other than magnesium on the secretion of thyrocalcitonin, either as stimulants of secretion or as modifiers of the response of the gland to hypercalcemia, do not appear to have received much attention as yet. 

Hypocalcemic perfusion of the pig thyroid in situ results in a slight rise in the systemic blood calcium level, which might be caused by a shutting-off of thyrocalcitonin secretion (C5). The normal level of thyrocalcitonin output might depend on the prevailing level of secretion of parathyroid hormone this possibility is supported by the observation that hypocalcemic perfusion of the thyroid in parathyroidectomized pigs was unaccompanied by the rise in systemic plasma calcium observed in intact animals. Until sensitive immunoassay procedures become more widely available, however, it is difficult to be sure whether or not thyrocalcitonin is secreted under resting conditions in the intact animal. A preliminary report of a radioimmunoassay technique for thyrocalcitonin, by Arnaud and Littledyke (A5), indicates that all plasma samples examined contained detectable thyrocalcitonin, and that thyroidectomy resulted in a decrease in thyrocalcitonin levels below those found in normal animals. 

It is an attractive concept that the uniformity of the plasma calcium concentration in health is attained through balanced low levels of secretion of both parathormone and thyrocalcitonin, and that disturbances of calcium homeostasis may result both in a reduction of the resting level of secretion of one hormone, and in a raised output of the other. Until both hormones can be assayed with precision, the possibility of such a dual mechanism, operating at physiological levels of plasma calcium variation, must remain somewhat speculative. 

Apart from variations in the response of different animal species to thyrocalcitonin injections or infusions, already described, different species might vary widely in the degree of hypercalcemia necessary to stimulate secretion of thyrocalcitonin. Care et al. (C6) reported that hypercal-cemic perfusion of the sheep thyroid produced a hypocalcemic response similar in magnitude to that obtained by Foster et al. (F4) during hyper-calcemic perfusion of the thyroid and superior parathyroid in a goat of... 

Significant differences in the apparent secretion of thyrocalcitonin might of course result from differences in the rate of destruction of the hormone, rather than from differences in its rate of secretion. A heat-labile factor that inactivates thyrocalcitonin has been found in plasma (T4), but its part in controlling the action of the hormone is as yet uncertain. 

Fiq. 6. The effect of exogenous thyrocalcitonin (TC) on the s3rstemic plasma calcium level during hypercalcemic perfusion of the thyroid in a methylthiouracil treated pig. [Redrawn from Duncan and Care (Dl).]... 

Gudmundsson et al. (G4) found that thyrocalcitonin produced no fall in calcium in parathyroidectomized rats, although the hypophosphatemic response was still present. If, however, the parathyroidectomized rats were previously fed a diet high in calcium and low in phosphate, so that... 

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