Control of the Thyroid Gland: Regulation of Its Normal Function and Growth

404 Pages·1989·9.732 MB·English

by  Jacob Robbins (auth.), Ragnar Ekholm, Leonard D. Kohn, Seymour H. Wollman (eds.)

CONTROL OF THE
THYROID GLAND
Regulation of Its Normal
Function and Growth
ADVA NCES IN EXPERIMENTAL MEDICINE AND BIOLOGY
Editorial Board:
NATHAN BACK, State University of New York at Buffalo
IRUN R. COHEN, The Weizmann Institute of Science
DAV ID KRITCHEVSKY, Wistar Institute
ABEL LAJTHA, N. S. Kline Institute for Psychiatrie Research
RODOLFO PAOLETTI, University of Milan
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CONTROL OF THE THYROID GLAND: Regulation of Hs
Normal Function and Growth
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CONTROL OF THE
THYROID GLAND
Regulation of Its Normal
Function and Growth
Edited by
Ragnar Ekholm
University of Göteborg
Göteborg, Sweden
Leonard D. Kohn
and Seymour H. Wollman
National Institutes of Health
Bethesda, Maryland
SPRINGER SCIENCE+BUSINESS MEDIA, LLC
Library of Congress Cataloging in Publication Data
Control of the thyroid gland: regulation of its normal function and growth / edited
by Ragnar Ekholm, Leonard D. Kohn, and Seymour H. Wollman.
p. cm. (Advances in experimental medicine and biology; v. 261)
Proceedings of a symposium held Mar. 20-21,1989, in Bethesda, Md.
Includes bibliographical references.
ISBN 978-1-4757-2060-0 ISBN 978-1-4757-2058-7 (eBook)
DOI 10.1007/978-1-4757-2058-7
1. Thyroid gland - Physiology - Congresses. 2. Thyroid gland - Growth - Con
gresses. 3. Growth factors-Physiological effect-Congresses. 1. Ekholm, Ragnar. II.
Kohn, Leonard D. III. Wollman, Seymour H.
[DNLM: 1. Receptors, Thyroid Hormone-physiology-congresses. 2. Thyroid
Gland - physiology - congresses. 3. Thyroid Hormones - physiology - congresses.
WK 202 C764 1989]
QP188.T54C66 1989
612.4/4-dc20
DNLM/DLC 89-23075
for Library of Congress CIP
Proceedings of a symposium on the Control of the Thyroid Gland:
Regulation of Its Normal Function and Growth, held March 20-21, 1989,
at the National Institutes of Health, in Bethesda, Maryland
© 1989 Springer Science+Business Media New York
Originally published by Plenum Press, New York in 1989
Softcover reprint of the hardcover 1s t edition 1989
AII rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
PREFACE
This volume presents the proceedings of a symposium
on the "Control of the thyroid gland~ regulation of its
normal function and growth," held at the National Insti
tutes of Health, Bethesda, Maryland on March 20 and 21,
1989.
Our motivation for the organization of this symposium
was the fast development in re cent years of our understan
ding of the regulation of the thyroid - and the progress
in the field of cell regulation in general - which have
led to profound modifications of our view of the control
of the thyroid. Not so many years aga the thyroid was
thought to be controlled by one regulator, the pituitary
TSH, which with cyclic AMP in the role of second messen
ger was considered to express or regulate most or all
processes in the gland. In the last several years it has
been weIl documented that hormones other than TSH and
various growth factors are involved in thyroid growth con
trol and it has been increasingly clear that several hor
mones and neurogenic agents are obligate participants in
the regulation of thyroid function. In addition, not only
new agonists acting on the thyroid have been revealed, but
new transducer and second messenger systems have been
discovered. In particular the interest has been - and is
focused on the signals emanating from the hydrolysis of
the inositol phospholipids, comprising the inositol tris
phosphate/Ca2~ pathway and the diacylglycerol/protein
kinase C pathway. Since these new signal systems must be
coordinated with the Hold" systems, the regulatory network
has become very complex. Parallel with the development of
these new areas in the field of thyroid regulation our
understanding of the TSH system has been modified and es
sentially improved with respect to the pituitary - thyroid
interrelation, the structure and function of TSH and the
structure and function of the TSH receptor.
v
PREFACE
The proceedings deal with almost all aspects of
thyroid regulation and surnrnarizes the current state of
our understanding of this biologically and clinically
important issue. We think that this volume will be a
valuable source of information not only to thyroid
ologists and endocrinologists in general, but also to
researchers in other fields who are interested in cell
regulation.
The Editors
CONTENTS
The Thyroid as a Model Endocrine System . . . . . . . 1
J. Robbins
THE PITUITARY-THYROID AXIS
What Controls Thyroid Growth - That Is, Thyroid Size . 5
L.J. DeGroot
The Pituitary-Thyroid Regulatory System 11
P.R. Larsen
Thyroid Stimulating Hormone: Structure and Function . 27
J.A. Magner
THYROID REGULATORS: NEUROGENIC AGENTS, HORMONES, IODIDE
Characterization of Receptors for Insulin and Insulin
Like Growth Factor-1 on FRTL-5 Thyroid Cells • 105
N. Perrotti, C.M. Rotella, F.V. Alvarez,
L.D. Kohn, and S. Taylor
Regulatory Peptides in the Thyroid Gland . . . . . . 121
T. Grunditz, F. Sundler, R. Hakanson,
and R. Uddman
Receptors of the Thyroid: The Thyrotropin Receptor Is
Only the First Violinist of a Symphony
Orchestra . . . . . . . . . . . . . . . 151
L.D. Kohn, M. saji, T. Akamizu, S. Ikuyama,
O. Isozaki, A.D. Kohn, P. Santisteban,
J.Y. Chan, S. Bellur, C.M. Rotella,
F.V. Alvarez, and S.M. Aloj
Excess Iodide Inhibits the Thyroid by Multiple
Mechanisms . • .. .. . • . • . . . . . . 211
J. Wolff
vii
viii CONTENTS
SIGNALS AND TRANSDUCTION
G Protein-Linked Receptors in the Thyroid • . • . • . 245
D. Corda, C. Bizzarri, M. Di Girolamo,
S. Valitutti, and A. Luini
ADP Ribosylation and G Protein Regulation in the
Thyroid . • . . . . . • . . . • • . . . • . . . 271
J.B. Field, F. Ribeiro-Neto, M. Taguchi,
W. Deery, C.S. Sheela Rani, and D. Pasquali
The Inositide and Arachidonic Acid Signal System . . 285
E.G. Lapetina
The Arachidonic Acid Signal System in the Thyroid:
Regulation by Thyrotropin and Insulin/IGF-I . . 295
K. Tahara, M. Saji, S.M. Aloj, and L.D. Kohn
REGULATION OF GROWTH AND FUNCTION
Integrated Regulation of Growth and Function . . . . 327
M.C. Eggo and G.N. Burrow
Regulation of Growth and Differentiation in
Follicle Cells . . . . . • . . . 341
M.C. Eggo, M.A. Christine Pratt, G.P. Becks,
and G.N. Burrow
Transducing Systems in the Control of Human Thyroid
Cell Function, Proliferation, and
Differentiation . . . . . . . . . . . . 357
J.E. Dumont, A. Lefort, F. Libert, M. Parmentier,
E. Raspe, S. Reuse, C. Maenhaut, P. Roger
B. Corvilain, E. Laurent, J. Mockel,
F. Lamy, J. Van Sande, and G. Vassart
Thyroid Specific Gene Expression . • . • • . . . . • 373
A.J. Sinclair, R. Lonigro, D. Civitareale,
and R. Di Lauro
Index . . . . . . . . . . . . . . • . • . . . . . . . 391
THE THYROID AS A MODEL ENDOCRINE SYSTEM
Jacob Robbins
NatIonal Institutes of Health, Bethesda, Maryland 20892
The focus of this conference is on the regulation of growth and
differentiated function of the thyroid gland. Dur expectation is that
the information and the insight that will be developed can serve as a
model for other endocrine organs and, even more broadly, might
contribute to an understanding.of the growth and function of any
specialized group of cells in a multi-cellular organism. In the
vernacular of our time, we speak of communication between cells by
chemical means. We know that this form of communication occurs at all
levels of the plant and animal kingdoms, from sex factors exchanged
between single yeast cells, to pheromones exchanged between insects,
and on to endocrine organs of higher animals whose chemical signals
are called hormones, and are transported to distant targets through a
circulatory system.
The boundary that separates endocrine signals from other types of
chemical communication is certainly arbitrary and constantly open to
redefinition. Classical endocrine systems, however, are of two
general types. The first are those that consist of a group of cells
that send and receive signals without the interposition of another
regulatory organ. Examples are the parathyroids and the pancreatic
islets whose secretory products are polypeptide hormones. A
subcategory consists of endocrine organs closely allied to the nervous
system. They include the posterior pituitary, which is composed of
neurons that secrete the neuropeptides, oxytocin and vasopressin, and
the chromaffin cells of the adrenal medulla that secrete epinephrine
and norepinephrine. The latter are analogous to sympathetic
post-ganglionic cells and have their embryonie origin in the neural
crest. Also derived from the neural crest are the thyroid
parafollicular cells, whose secretory product is calcitonin. Although
2 J. ROBBINS
the thyroid could thus serve as a model neuroendocrine organ, this
will not be our concern in this symposium.
The second type of endocrine system, to which the thyroid
follicular cells belong, does have an interposed regulatory organ.
Besides the thyroid, these include the ovary, the testis and the
adrenal cortex and they have a number of features in common. First,
they are all under the control of hormones secreted by the anterior
pituitary gland, that are themselves regulated by neuropeptide
hormones derived from the central nervous system. Second, the thyroid
stimulating hormone and the gonadotrop ins (but not ACTH) are
glycoproteins with extensive sequence homology. Third, the hormones
that these glands secrete have relatively slow actions on growth and
development, actions that are mediated through effects on protein
synthesis. All of these hormones are small molecules either
steroids or, uniquely in the case of the thyroid, amino acids. Their
effects on the cell nucleus are achieved through an homologous set of
DNA-binding receptor proteins that are the products of genes related
to the erb-A protooncogene.
The evolutionary implications of these homologies are still a
mystery and extend beyond these particular endocrine systems. Thus,
the pituitary gonadotropic hormones are also related to the chorionic
gonadotrop in of the placenta. All of the glycoprotein hormones,
including TSH, are dimeric molecules that share an identical a subunit
but have distinct ß subunits that account for their individuality. 1t
has been suggested that this protein family arose by gene duplication
of a primitive a chain with subsequent duplications and sequence
divergence of the ß-chains during vertebrate evolution.
The extensive erb-A related protein family includes, in addition
to the receptors for all the steroid hormones and the thyroid hormone,
the receptors for vitamin D and retinoic acid as weIl. These receptor
molecules share a common DNA-binding region but diverge in their
hormone-binding domains. Clearly they must have a common origin. The
mystery of these kinds of relationships is certainly not unique to
endocrinology and continues to deepen as the lexicon of protein and
gene sequences expands geometrically. 1t motivates us to search for
analogies in previously unrecognized relationships and is certain to
lead to new insight that might not otherwise have reached a conscious
level. Hopefully this symposium will provide us with some flashes of
recognition.
The complexity of the thyroid system ensures that the subjects to
be discussed will be wide ranging. Although we are not concerned here
with the action of thyroid hormone at its distant targets, the
negative feedback at the pituitary is an important aspect of thyroid
regulation. Is the mechanism of thyroid hormone action on the
pituitary thyrotrophs analogous to its action in the periphery? There
are reasons to believe that multiple mechanisms for thyroid hormone