J Physiol Pharmacol 2002;46 (4);
Endocrinology in The Last Century
SURESH V. SAGARAD
Department of Cardiology,
K. G. Medical College,
Lucknow – 226 003
the most primitive forms of life regulate the expression of their
genetic material in a complex manner. With increasing differentiation
of structure and function in the course of evolution, regulation
mechanisms have assumed increasing importance in the survival of
the organisms, in its adaptation to the environment and in its reproduction.
The two primary communication systems, the nervous system and the
endocrine system, serve as the biological communication network
for integration of the organism’s response to a changing environment.
molecules traverse the extracellular space to aid in cell-cell communication.
Cells communicate with themselves, with nearest neighbours, with
distant cells via a circulatory system, and with separate organisms
across an intervening “environment”. These types of cell communication
are designated as autocrine, paracrine, endocrine, and pherocrine,
respectively. The biological beginnings of these processes probably
occurred with the transition from unicellular to multicellular organisms
having sufficient size to prohibit direct communication among all
to unravel this tangled scheme began a mere 2500 years ago with
the beginning of free inquiry in the city of Greece. The development
of our understanding of the endocrine system closely parallels the
evolution of the physical and biological sciences across the intervening
years. Earlier works in this field can be traced to 400 BC. Aristotle
had described the effects of castration on the songbird (1). 400
years later Galen described and named the thyroid gland in dissections
of great apes and perhaps in humans (2).
work has restricted to anatomical (3, 4). Physiological details
started appearing in the literature at the end of 19th Century
when Claude Bernard demonstrated the process of “internal secretion”
(5). The question as to the mechanisms by which a pancreatic secretion
is evoked by the introduction of acid into the duodenum led to the
identification of messenger molecules. Pavlov noted that the secretion
evoked by the presence of acid in the duodenum as reflex in origin,
and thought the varying composition of the juice in different diets
to a marvelous sensibility of the duodenal mucous membrane, so that
different constituents of the chyme excite different nerve endings,
or produce correspondingly different kinds of nerve impulses, which
travel to the gland or its nerve centers, and determine the varying
activity of the gland cells (6).
Pavlov’s observations, Popielski (7), and Wertheimer and Lepage
(8) showed during 1900 – 1901 that the introduction of acid into
the duodenum excites pancreatic secretion even after section of
both vagi and splanchnic nerves or destruction of the spinal cord
and even after extirpation of solar plexus. Popielski concluded,
therefore, that the secretion was due to a peripheral reflex actions,
the centers of which are situated in the scattered ganglia found
throughout the pancreas and ascribed special importance to a large
collection of ganglion cells in the head of the pancreas close to
and Lepage, while accepting Popielski’s explanation of the secretion
excited from the duodenum, found that secretion could also be induced
by injection of acid into the lower portion of the small intestine,
the effects, however, gradually diminishing as the injection was
made nearer the lower end of the small intestine, so that no effect
at all was produced from the lower two feet or so of the ileum.
Secretion could be excited from a loop of jejunum entirely isolated
from the duodenum. They concluded that, in the latter case the reflex
centers are situated in the ganglia of the solar plexus, but they
did not perform the obvious control experiment of injecting acid
into an isolated loop of jejunum after extirpation of these ganglia.
They also showed that the effect was not abolished by injection
of large doses of atropine, but compared with this the well known
insusceptibility to this drug of the sympathetic fibres of the salivary
apparent local character of this reaction interested Bayliss and
Starling (9) to make further experiments in the subject, in the
idea that they might have to do with an extension of the local reflexes
whose action on the movements of the intestines they had already
investigated. They soon found, however, that they were dealing with
an entirely different order of phenomenon, and that the secretion
of the pancreas was normally called into play not by nervous channels
at all, but by a chemical substance which is formed in the mucous
membrane of the upper parts of the small intestine under the influence
of acid and is carried thence by the blood stream to the gland-cells
of the pancreas. They called the substance “secretin”. Molecules
with this property, stimulating a response in a distant organ via
the blood stream, were first referred to as hormones, from the Greek
hormoao (to excite), by Professor Starling in 1905 in his
Croonian Lectures to the Royal College, “The Chemical Correlation
of the Functions of the Body”. Thus the modern era of endocrinology
began. As the physiological basis of many endocrine diseases were
discovered, the biochemists’ efforts to isolate and purify the hormones
continued: thyroxine, cortisone, insulin, and the list continues.
purification and therapeutic usage demanded development of measurement
systems like radioimmunoassay by Berson and Yallow in 1969 (10).
Measurements of hormones at various stages in biological system
revealed the fluctuating nature which stimulated the study of endocrine
physiology, particularly, “feedback regulation” of hormone secretion.
understanding of the mechanisms of hormone action led to new vistas
in the era of investigative endocrinology like cellular biology
of hormones action, receptor structure and function, signal transduction,
gene regulation, peptide processing, and the mechanisms of hormone
secretion. As of now, the general scheme is that the hormones mediate
their action via second messenger systems and these second messengers
are involved in the specific cascade of events set in motion by
the hormone-receptor interaction that leads to an alteration in
the concentration of molecular species interacting with hormone-responsive
gene regulatory elements.
over a hundred years of work in this field, we now know that gland,
hormone, transport, action and feedback are the fundamental attributes
of the endocrine system. There are nine classic glands (hypothalamus,
pituitary, thyroid, Parathyroid, pancreas, adrenal, tests and ovary)
and an ever-increasing number of non-classical glands (thymus, heart
gut, kidney, placenta, skin) that secrete hormones. Ever since the
identification of secretin, the number of new hormones added to
this list has increased, both in the lipid soluble group and the
is now hundred years since March 1902, when Bayliss and Starling
conducted their crucial experiments, which elucidated the mechanism
of control of pancreatic secretion and discovered ‘Secretin’. This
last century has seen the development of endocrinology in various
fronts. Despite understanding the complexities of this field, we
are left with many areas unsurfed. No doubt, new molecules will.
Be added to the list and exploration in second messenger pathways
Aristotle. Historical Animalium, Book 9, volume 4. (As given
in reference no. 9).
Sarton G. Galen of Pergamon. Lawrence, University of Kansas
Vesalius A. De Humanis Corporis Fabricas, Basel, 1543.
Eustachius B. Opseula Anatomica, Venice, 1563.
Loriaux DL, Claude Bernard. The Endcorinologist 1891; 1:
Pavlov. Die Arbeit Verdauungsdrusen. Trans. From Russian.
Popielski. Gazette Clinique de Botkin (Russ) 1900.
Wertheimer and Lepage. Journal de Physiologie 1901;
Bayliss WM, Starling EH. The mechanism of pancreatic secretion.
J Physiology 1902; 28: 325-353.
Berson SA, Yalow RS, Radioimmunoassay of peptide hormones
in plasma. N Engl J Med 1967; 277: 640-647.