Table Of ContentEndocrinology
PEOPLE AND IDEAS
CENTENNIAL CELEBRATION COMMITTEE
A. P. FISHMAN, Chairman L. L. LANGLEY
P. A. CHEVALIER S. OCHS
J. S. COWAN A. B. OTIS
M. FRANK (EX OFFICIO) M. C. SHELESNYAK
D. L. GILBERT H. V. SPARKS, JR.
P. C. JOHNSON (EX OFFICIO) N.C. STAUB
R. J. C. JOY J. B. WEST
R. H. KELLOGG
PUBLICATIONS COMMITTEE
P. c. JOHNSON, Chairman
J. S. COOK
W. F. GANONG
L. R. JOHNSON
J. MCE. MARSHALL
B. B. RAUNER, Publications Manager and Executive Editor
L. s. CHAMBERS, Production Manager, Books
A. P. BARRETT, s. P. MANN, Editorial Staff
Endocrinology
PEOPLE AND IDEAS
Edited by S. M. McCann
Springer New York
ISBN 978-1-4614-7436-4 (eBook)
DOI 10.1007/978-1-4614-7436-4
©Copyright 1988, American Physiological Society
Originally published by American Physiological Society in 1988
Softcover reprint of the hardcover lst edition 1988
Library ofCongress Catalog Card Number: 87-18855
International Standard Book Number: 0-19-520718-1
Preface
T
HIS book grew out of suggestions from the Publications Com
mittee of the American Physiological Society, which has planned
a series covering the development of ideas about a number of areas
of physiology. This was prompted by the great success of Circulation
of the Blood: Men and Ideas, edited by A. P. Fishman and D. W.
Richards, which was originally published in 1964 and then reissued
by the Society in 1982. Three companion books are being completed
in conjunction with the centennial year of the American Physiolog
ical Society: this volume on endocrinology, one on the kidney, and
one on membrane transport.
It was our purpose not to provide a complete bibliography or a
complete listing of all the progress made in a given area but to show PREFACE
the principal ideas and how they developed. Consequently, limita-
tions were placed on the number of references and on the length of
each chapter. This book covers most of the areas of endocrinology;
it is not completely comprehensive but discusses the main pathways
of development and highlights the prominent investigators. We hope
that the book as a whole will give an excellent picture of the evolution
of this exciting area of physiology and the people involved in its
growth.
Most of the endocrine organs were discovered in antiquity by such
early workers as Aristotle and Galen. The last endocrine gland to be
discovered was the parathyroid in 1891 by Gley.
In ancient times Aristotle wrote of the effects of castration on the
behavior of the hog; he also noticed that the ovaries of sea urchins
waxed and waned with the lunar cycle. Galen, the Greek physician
who lived in Alexandria, Egypt, around the time of Christ, developed
the concept that the pituitary gland was a secretor of animal spirits
through the sphenoid and into the nose. These primitive concepts of
endocrine function persisted even until the sixteenth century, when
Descartes claimed that the pineal gland was the seat of the soul.
The first evidence for an endocrine function was provided by
Berthold, who transplanted testes into castrated roosters, which
resulted in maintenance of comb size, crowing, and other signs of
masculine behavior. This fundamental advance was followed by
similar experiments in the female by Knauer in 1895 indicating that
the growth of the uterus and vagina could be maintained by ovarian
I vI
transplants. At this same time, Minkowski transplanted the pancreas
into depancreatized dogs and showed that diabetes mellitus was
ameliorated.
The next step was to make extracts of endocrine organs. One of
the first to do this was Brown-Sequard, who injected himself with
aqueous extracts of bull testes and claimed that they rejuvenated
ENDOCRINOLOGY
him. Unfortunately, in retrospect these were probably placebo ef
fects, but they stimulated others to make aqueous extracts; indeed it
was shown in 1891 that thyroid powder would correct the deficien
cies of myxedema, adult hypothyroidism.
Endocrinology has always been intimately linked with clinical
medicine. During the nineteenth century most of the clinical entities
were discovered. For example, Addison described Addison's disease
as a deficiency of the adrenal cortex in 1855. In 1895 Marie de
scribed acromegaly, the first example of hyperfunction of an endo
crine gland, which was shown to be due to eosinophilic adenomas of
the anterior pituitary gland. Oliver and Sharpey-Schiifer made
aqueous extracts of the adrenal gland in 1895 and found that they
had pressor activity, thus discovering epinephrine. In that same year
they made extracts of the pituitary gland and showed that they also
had pressor activity; the oxytocic activity was revealed shortly there
after.
The next breakthrough of practical significance was the prepara
tion by Collip of insulin in a form suitable for injection into patients
after the discovery of the hormone by Banting and Best. This intro
duced insulin treatment for diabetes mellitus, one of the commonest
endocrine diseases. Parathyroid hormone, one of the last of the
nonsteroid hormones to be extracted, was prepared in 1925 by
Collip. Aqueous extraction proved adequate for the extraction of the
hormones that were small organic compounds, such as epinephrine
and thyroid hormone, and for various peptide and protein hormones;
however, it was not adequate for the lipid-soluble steroid hormones.
Allen and Doisy were the first to make lipid extracts of ovaries that
contained estrogen. This was followed quickly by the preparation of
similar extracts from testes and finally in the 1930s from the adrenal
cortex.
The next step was to isolate these new compounds, determine
their structure, and synthesize them. This was fairly easy for rela
tively simple compounds, such as epinephrine and thyroxine, and
the saga of the attempts to synthesize thyroxine is described in this
volume.
Further developments in organic chemistry allowed the elucida
tion of structure of the steroid hormones during the 1930s. Even
here a new technique, paper chromatography, was necessary to
separate aldosterone from the other adrenal steroids in the 1950s.
Advances in peptide chemistry finally allowed the structural elu
cidation of the first two brain peptides, oxytocin and vasopressin, by
[ VI ]
DuV igneaud in the 1950s. Elucidation of the structure of the larger
anterior pituitary hormones such as adrenocorticotropin, growth
hormone, and prolactin continued until the early 1970s. The hypo
thalamic peptides were discovered in the 1950s and 1960s, and their
structures were determined between 1969 and 1983. The elucida
tion of their structures was hindered by the fact that there were very
PREFACE
small stores of these peptides in the hypothalamus, necessitating
fractionation of millions of glands to obtain enough material for
analysis. Dramatic progress in peptide chemistry in the intervening
years has greatly reduced the quantity of peptide required for
elucidation of structure. Thus the structure of many gastrointestinal
peptide hormones has been determined, particularly by Mutt's group
in Stockholm.
Finally, developments in molecular genetics made possible the
elucidation of the structure of some larger peptides, the first of
which was the pro-opiomelanocortin molecule. These techniques
have now been used to determine the structure of more complex
hormones, such as gonadotropins and inhibin, the gonadal inhibitor.
After the discovery of a new hormone, physiologists have worked
out the control systems involved and studied the actions of the
hormone on its target tissues. Pharmacologists have been involved
in the production and testing of analogues with inhibitory or agonistic
action. An area of investigation that has grown rapidly in the last few
years is the mechanism of action of hormones. In every case this
involves interaction with a receptor. The receptors are usually on
the cell surface; however, the receptors for thyroid hormones and
steroid hormones are in the cytosol and carry the hormone to the
nucleus, where it interacts with DNA to evoke messenger RNA
synthesis. The other hormones act on the receptors, which results in
second-messenger effects, such as the activation of adenylate cyclase.
The complexity of the action of hormones has been revealed in
recent studies showing that often this also involves cyclic GMP, the
phosphatidyl inositol cycle, arachidonic acid metabolites, and extra
cellular and intracellular calcium.
It is obvious from this brief introduction that the development of
endocrinology has involved an intertwining of information obtained
through clinical medicine with physiology, biochemistry, and ge
netics to discover a host of hormones, unravel their structure, and
determine their function and mechanism of action. The number of
hormones is still increasing; because of the extraordinarily rapid
elucidation of the structure and function of atrial natriuretic peptide,
we include a chapter to show the contrast between its development
and that of hormones discovered earlier. Atrial natriuretic peptide
went from discovery to synthesis and study of its mechanism of
action within four years.
This book begins with a discussion of vasopressin and then exam
ines the development of concepts in the control of pituitary hor-
(VII j
mones and their target glands. It also considers the neural lobe of
the pituitary gland and the pineal gland, which are completely under
neural control. It continues with various pituitary hormones under
neural control, such as the gonadotropins and prolactin. Discussion
then shifts to the pituitary target glands, such as the adrenal gland,
thyroid, and ovary. The book then moves to consideration of periph
ENDOCRINOLOGY
eral hormones, such as parathyroid hormone and calcitonin, and the
pancreatic hormones. This is followed by a description of the mech
anism of action of hormones, a very active field, and includes a brief
discussion of hormone receptors. The next chapter reviews receptors
and the receptor concept in depth. Finally, the newly discovered
atrial natriuretic peptide is considered and a brief description of the
development of concepts in comparative endocrinology is provided.
S.M. McCANN
[ VIII ]
Table of Contents
Vasopressin and Regulation of Water
I
Homeostasis and Cardiovascular Function 1
LEONARD SHARE
II Anterior Pituitary Neural Control Concepts 23
CHARLES H. SAWYER
III Saga of the Discovery of Hypothalamic
Releasing and Inhibiting Hormones 41
S.M. McCANN
Gonadotropins 63
IV
ROY 0. CREEP
v Pituitary-Adrenal System 87
DON H. NELSON
VI Prolactin 117
JOSEPH MEITES
Defining Thyroid Hormone: Its Nature
VII
and Control 149
CLARK T. SAWIN
Endocrine Function of the Ovary 201
VIII
KENNETH J. RYAN
Pineal Gland 215
IX
RUSSEL J. REITER AND
MARY K. VAUGHAN
[ ix ]
