Table Of ContentCALCITONIN
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.)
