Calcitonin. Proceedings of the Symposium on Thyrocalcitonin and the C Cells, London, 17–20 July 1967 PDF
Preview Calcitonin. Proceedings of the Symposium on Thyrocalcitonin and the C Cells, London, 17–20 July 1967
CALCITONIN Proceedings of the Symposium on Thyrocalcitonin and the C Cells London, 17-20 July 1967 WILLIAM HEINEMANN MEDICAL BOOKS LTD LONDON First published 1968 © William Heinemann Medical Books Ltd, 1968 Printed in Great Britain by Robert MacLehose & Co. Ltd, The University Press, Glasgow PRESIDENT SIR JOHN MCMICHAEL ORGANISING COMMITTEE PROFESSOR IAIN MACINTYRE Chairman DR. GIRAUD V. FOSTER Secretary PROFESSOR A. G. E. PEARSE Treasurer MR. SELWYN TAYLOR Editor PROFESSOR RUSSELL FRASER Acknowledgements The Organising Committee wish particularly to thank the Wellcome Trust for generous financial support, without which it would not have been possible to hold the Symposium. Generous support has also been given by: American Cyanamid Company Armour Pharmaceutical Co. (U.S.A.) Armour Pharmaceutical Co. Ltd. (England) Ciba Limited Evans Medical Limited Nicholas Laboratories Limited Nitrate Corporation of Chile Limited Organon Laboratories Limited Paines and Byrne Limited Sandoz Limited and Schering A.G., Berlin who made a donation specifically to defray the cost of publishing these Proceedings. Introduction The Symposium on Thyrocalcitonin and the C Cells which was held at the Royal Postgraduate Medical School, 17-20 July 1967, was attended by three hundred and fifty delegates, most of whom were active research workers in this field. The result of their deliberations, published here, provides the most comprehensive and up to date account of calcitonin presently available. Calcitonin, thyrocalcitonin, C Cells; all these terms have usually been left exactly as they appeared in the original manuscripts. However, many expressed a preference for the original shorter name of calcitonin for this calcium lowering hormone, since the C Cells derive from the ultimobranchial body and this may develop quite separately from the thyroid gland as in birds, or become incorporated in the thyroid gland as in mammals. For this reason the title of this publication incorporates both terms, calcitonin and thyro- calcitonin. Occasionally, it will be noted that the words in the illustrations do not marry with the text and this is because after blocks had already been made some authors preferred to change the text. This is probably a good thing in that it faithfully reflects thought and work in the field at present. Because this volume will prove to be a valuable reference work it has been published with all speed and any errors or omissions should be excused. The large number of tables, graphs and histological preparations have had to be rationed, but it is hoped without spoiling the text. The publication of a volume such as this would not be possible without the skilled assistance of many people, I must however give especial thanks to Iain Maclntyre, who has been a tower of strength in assisting with the preparation of the material for the printers. Miss Martyn of William Heinemann Medical Books has also performed an excellent task in seeing the work through the press. The Organising Committee wish to express their thanks to the Wellcome Trust and all those organisations who, by their generous gifts, made this conference possible and the publication of its proceedings. Last, but not least, Miss Margaret Pollard, the Organising Secretary deserves our especial thanks. SELWYN TAYLOR R.P.M.S. Hammersmith Hospital London W. 12 List of Authors Aldred, J. P. Gudmundsson, T. V. Pearse, A. G. E. Antonozzi, I. Perault-Staub, A. M. Au, W. Y. W. Hachmeister, U. Pfeiffer, E. F. Aurbach, G. D. Harman, R. E. Phillippo, M. Azzali, G. Hinde, F. Potts, J. T. Hioco, D. Putter, I. Barnes, N. D. Hirsch, P. F. Bastian, J. W. Holt, S. J. Raisz, L. G. Belanger, L. F. Ramberg, C. F. Bell, N. H. Joplin, G. F. Reisfeld, R. A. Bell, P. H. Jowsey, J. Reynolds, J. J. Bellavia, J. Rickes, E. Bonicke, J. Kahnt, F. W. Robinson, C. J. Bordier, Ph. Kaczka, E. A. Rothrock, J. W. Breustedt, H.-J. Kempf, A. J. Russell, R. G. G. Bronner, F. Klein, D. C. Buckle, R. M. Kracht, J. Sammon, P. J. Bussolati, G. Kronfeld, D. S. Sampietro, R. Byfîeld, P. G. H. Kuczerpa, A. V. Schlueter, R. J. Kueh, Y. Shah, B. G. Capen, C. C. Kumar, M. A. Sherwood, L. M. Carvalheira, A. F. Smith, R. N. Chaiet, L. Laljee, H. C. K. Solcia, E. Chan, A. S. Lenke, M. Stern, P. Chausmer, A. Sturtridge, W. C. Clements, G. R. Maclntyre, I. Sundler, F. Cockcroft, D. W. Martin, T. J. Coen, G. Matrajt, H. Talmage, R. V. Colwell, J. A. Mayer, G. P. Tashjian, A. H. Copp, D. H. Mazzuoli, G. F. Thalassinos, N. Melville, M. Thesingh, C. W. Dailey, J. P. Milhaud, G. Tsien-Ming, L. Dingle, J. T. Mittleman, R. Tun-Chot, S. Dorrington, K. J. Moukhtar, M. S. Wallach, S. Doyle, F. H. Munson, P. L. Warnock, D. R. Wase, A. W. Fleisch, H. Neher, R. Wasthed, A. B. Flitney, F. W. Nesralla, H. Wazeter, F. X. Fossieck, B. Niemann, I. Welsch, U. Foster, G. V. Nisbet, J. Wolf, F. J. Fraser, T. R. Nordin, B. E. C. Woodhouse, N. J. Y. Friedman, J. Nunez, E. A. Woodward, P. M. Gaillard, P. J. Owman, C. Young, D. M. Galante, L. Gould, R. P. Parsons, J. A. Ziegler, R. Calcitonin: An Introductory Review I. MACINTYRE Royal Postgraduate Medical School, Hammersmith Hospital, Ducane Road, London, W.Y1 This introduction is for those who are not familiar with the field. I have divided it into five sections: the existence of calcitonin; its source; aspects of purification; the mode of action of the hormone; its effect in man. Most leading workers are participating in this meeting and, therefore, I shall not cover the literature completely. Rather, our present knowledge will be summarised so that the new work to be presented later will be seen in perspective. THE EXISTENCE OF CALCITONIN Plasma calcium is regulated with great precision. It was held until recently that this was achieved by appropriate alteration in the secretion rate of the parathyroid hormone (McLean and Urist, 1961). Thus, a fall in plasma cal- 006 THYRO-PARATHYROID PERFUSION Carotid •Systemic Artery Vein Thyro-parathyroid 'Low Calcium Blood High Calcium FIG. 1. Dog thyroparathyroid perfusion system. The contralateral thyroid and parathyroid glands are removed. Alternatively the glands can be perfused with low-calcium blood, in which case high-calcium blood is infused via the systemic vein. 2 I. MACINTYRE cium would increase the secretion rate, tending to correct the fall; conversely, a rise in plasma calcium would produce inhibition, so lowering the calcium to normal. Early experimental work designed to test this hypothesis (Patt and Luck- hard t, 1942) was weak, and Copp and colleagues (Copp, Cameron, Cheney, Davidson and Henze, 1962) were the first to apply an adequate test. Their WHO-PARATHYROID PERFUSION LOW CALCIUM HI6H CALCIUM O 6 00 100 200 100 200 300 Time (min.) Time (min.) WRO-PARATHYROID PERFUSION NI6N CALCIUM LOW CALCIUM 100 200 100 200 Time (min.) Time (min.) FIG. 2. The effect of hypercalcaemic and hypocalcaemic thyroparathyroid per- fusion on systemic arterial plasma calcium level in four dogs. (From Kumar, Foster and Maclntyre, Lancet, 1963.) work is the real starting point. They carried out perfusion experiments in the dog and had the courage to postulate the existence of a new calcium-lowering hormone which they called 'calcitonin'. However, Copp also concluded that the hormone came from the parathyroid glands. We shall see shortly that this second deduction was wrong. I shall now refer to perfusion experiments from my own laboratory, con- firming that a new hormone must exist. A full description has been published (Kumar, Foster and Maclntyre, 1963; Maclntyre, Foster and Kumar, 1965) Introductory Review 3 but the experimental technique and results are illustrated in Figs. 1, 2 and 3. High-calcium perfusion of the dog thyroparathyroid glands produced a more rapid fall in systemic plasma calcium than total thyroparathyroidectomy. This proved conclusively that a new hormone existed, although our studies did not tell us whether the thyroid or parathyroid glands were the source. CONTROL PERFUSIONS LOW CALCIUM 5 20 500 5 50 r 5 30 5 10 A9Û 100 200 300 Time (min.) FIG. 3. Control experiments in two dogs in which the thyroid and parathyroid glands on the experimental side were removed immediately before the perfusion with high-calcium blood, so that these animals were totally thyroparathyroidecto- mized. Compare with Fig. 2. (From Kumar, Foster, and Maclntyre, 1963.) THE SOURCE OF CALCITONIN (a) The gland I shall now present evidence that the hormone is secreted by the thyroid and not the parathyroid glands, as Copp and colleagues first thought. To dis- tinguish between the glands it was necessary to repeat the dog perfusion ex- periments in a species in which the thyroid and parathyroid glands could be perfused separately. This was done in the goat, and the results are seen in Figs. 4 and 5. A fall in systemic plasma calcium occurred only when the thyroid was perfused. Perfusion of the parathyroid alone produced no effect. These results are unequivocal. They show that calcitonin is of thyroid origin and that it is secreted by the thyroid when this gland is perfused with high- calcium blood (Foster, Baghdiantz, Kumar, Slack, Soliman, and Maclntyre, 1964). It is also clear that calcitonin is identical with thyrocalcitonin. This is the provisional name given by Hirsch, Gauthier and Munson (1963) to the principle responsible for the calcium-lowering effect they first observed after the injection of crude rat thyroid extract. At first these conclusions were treated with reserve (Copp, 1965) or were even resisted with some acerbity (Schwartz, 1965). However, it now seems generally agreed (Copp, personal communication; Munson and Hirsch, 1966) that 'calcitonin' and 'thyrocalcitonin' are synonymous terms. I still hold the view (Maclntyre, Foster and Kumar, 1965) that the original name 'calcitonin' is preferable, but I think this is a decision which should be reached by inter- 4 I. MACINTYRE ^ Him CALCIUM FIG. 4. Schematic diagram of areas perfused in goats. In each instance all contra- lateral thyroid and parathyroid tissue was removed before the control period. (a) Isolated, perfused segment of the common carotid artery. The internal para- thyroid is not visible to the naked eye. (b) Isolated, perfused carotid artery segment after removal of the thyroid. The thyroid was removed at the same time as the glands on the other side. (From Foster et ai, 1964.) <q -0-80 30 60 90 120 150 TIME (Minutes) FIG. 5. Hypercalcaemic perfusion of the isolated external parathyroid (·-·) and total thyroparathyroid apparatus (O- O ) in goats. Curves represent mean values with standard errors of changes in systemic plasma calcium from the control values. Five goats were used in each group. (From Foster et al., 1964.)
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