Endocrinology in The Last Century

SURESH V. SAGARAD
Department of Cardiology,
K. G. Medical College,
Lucknow – 226 003

Even 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.

Messenger 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 constituent cells.

Attempts 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).

Subsequent work has restricted to anatomical (3, 4). Physiological details started appearing in the literature at the end of 19^th 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).

After 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 the pylorus.

Wertheimer 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 glands.

The 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.

Isolation, 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.

Further 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.

After 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 water-soluble group.

It 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 will continue.

REFERENCES 

1.       Aristotle. Historical Animalium, Book 9, volume 4. (As given in reference no. 9).
2.       Sarton G. Galen of Pergamon. Lawrence, University of Kansas Press, 1954.
3.       Vesalius A. De Humanis Corporis Fabricas, Basel, 1543.
4.       Eustachius B. Opseula Anatomica, Venice, 1563.
5.       Loriaux DL, Claude Bernard. The Endcorinologist 1891; 1: 362-363.
6.       Pavlov. Die Arbeit Verdauungsdrusen. Trans. From Russian. Wiesbaden 1898.
7.       Popielski. Gazette Clinique de Botkin (Russ) 1900.
8.       Wertheimer and Lepage. Journal de Physiologie 1901; 3: 335.
9.       Bayliss WM, Starling EH. The mechanism of pancreatic secretion. J Physiology 1902; 28: 325-353.
10.   Berson SA, Yalow RS, Radioimmunoassay of peptide hormones in plasma. N Engl J Med 1967; 277: 640-647.