William Maddock Bayliss and Ernest Henry Starling proved unequivocally that chemical integration can occur in the body without assistance from the nervous system.
Much information is available today concerning the control of secretin
Bayliss and Starling subsequently discovered that the signal is chemical in nature, not nervous. The arrival of acid-laden food causes the intestinal wall to secrete a substance called secretin, which oozes into the bloodstream. Physiologists know that secretin causes the pancreas to secrete a solution high in bicarbonate, which has the effect of buffering hydrochloric acid. Secretin also tends to inhibit motility of the stomach while stimulating the secretion of pepsin (an enzyme that breaks specific internal peptide bonds in a protein). Secretin is the single most important inhibitor of gastrin release and therefore of acid secretion.
Starling first used the word “hormone” (from the Greek hormon, meaning exciting, setting in motion) in 1905 with reference to secretin. Today, physiologists know that hormones may inhibit as well as excite. Hormones do not initiate metabolic transformations; rather, they merely alter the rate at which these changes occur. Bayliss and Starling also developed the concept that powerful chemical messengers exist in the common pool of blood and lymph.
Secretin has been obtained in crystalline form and is a basic polypeptide. The hormone disappears rapidly from circulation owing to the destructive action of an enzyme called secretinase. Small amounts of the hormone are excreted in the urine. Many materials other than hydrochloric acid stimulate the release of secretin by the duodenal mucosa; water, alcohol, fatty acids, partially hydrolyzed protein, and certain amino acids are all effective.
The crude extract that Bayliss and Starling used in their experiment caused the pancreas to secrete enzymes as well as water and bicarbonates. Because purified secretin seemed to stimulate only the output of water and bicarbonate, researchers began to look for the material in the extract that stimulated secretions of the enzymes. In 1943, A. A. Harper and H. S. Raper succeeded in separating a fraction that did not increase the volume of pancreatic juice but greatly increased the enzyme concentrations. This substance was called pancreozymin. In 1966, in the course of their purification of cholecystokinin
It is now known that actions of secretin and CCK are not as completely separate as previously believed. Secretin augments the action of CCK on pancreatic enzyme secretions, and CCK augments the action of secretin on bicarbonate ion secretions. This augmentation is important in the stimulation of pancreatic fluid when the pH of the duodenum, which is well buffered, does not fall significantly with the entry of a meal into the upper gastrointestinal tract. After secretin and pancreozymin became available in injectable form, tests of pancreatic function were developed that use these hormones as stimuli.
After secretin became available in a form pure enough for use in humans, researchers accumulated more experience with it. G. Agren et al. introduced the secretin test in 1936, and it has been used extensively in the United States and abroad. In this test, a double-lumen tube is passed through the patient’s nose or mouth into the stomach to drain gastric juice and into the duodenum to collect the pancreatic and duodenal secretions. The gastric and duodenal secretions are collected separately; gastric juice is usually aspirated continuously through the use of a low-pressure vacuum pump, whereas the duodenal contents are aspirated periodically. Volume, pH, bicarbonate, and enzyme determinations are made on the samples collected from the duodenum. With normal function, there is a rapid increase in flow rate following secretin injection, the maximum flow rate usually being reached in twenty minutes. A flow rate of 1 to 2 milliliters per kilogram of weight per thirty minutes is usually obtained in normal individuals. The bicarbonate concentration increases with the flow rate and may go as high as 140 to 150 milligrams per liter. As the flow rate increases, there is an associated decrease in enzyme concentration. When pancreozymin is used as a stimulus for pancreatic secretion to test pancreatic function, the procedure is the same as that described for the secretin test.
William Maddock Bayliss.
Secretin increases the secretion of bile by the liver, although it does not cause the gallbladder to contract. The site of action of secretin is thought to be the small bile ducts, or ductules. The effect results in an increase in the volume of bile by addition of water and a marked increase in the bicarbonate concentration. The onset of effect is similar to that of the pancreas. Some evidence suggests that an electrolyte fraction may be secreted that is dependent on the active transport of sodium and is inhibited by inhibitors of ATPase. Secretin causes only a moderate increase in bile flow and none at all if the liver is secreting vigorously already.
The pancreas is under the control of both nervous and humoral mechanisms. The nervous control of pancreatic secretion is provided by both the sympathetic and parasympathetic divisions of the autonomic nervous system. Humoral control of pancreatic secretion is provided by the hormones secretin, CCK, and gastrin. Atropine is said to block the effects of sympathetic stimulations, causing an increase in flow rate, indicating that cholinergic secretory fibers are present in the sympathetic innervation of the pancreas. Stimulations of the vagus, or parasympathetic innervation of the pancreas, result in the secretion of enzymes but have little or no effect on the secretions of bicarbonate. Acetylcholine is the mediator of the vagal effect. Vagotomy and atropine markedly depress the secretions of enzymes by the pancreas. Cholinergic drugs, such as pilocarpine, stimulate pancreatic secretion, whereas atropine and anticholinergic agents produce inhibitions.
Bayliss and Starling’s discovery relative to the existence and manner of action (at the level of the whole organism) of the hormone secretin was far-reaching. Ivan Petrovich Pavlov,
The islets of Langerhans
In 1949, Thomas R. Forbes reviewed the work of Arnold Berthold in a paper read before the Beaumont Club at Yale University. In the mid-nineteenth century, Berthold caponized six young cockerels and then returned single testes to the body cavities of some of the birds. The grafts, placed among the intestines, became vascularized. Berthold observed that the host birds continued to exhibit the sexual behavior and accessories of normal young roosters. At autopsy, he found that the nerve supply of the grafted testes had not been reestablished. He thus concluded that, as maintenance of sexual behavior and appearance could not have been accomplished by the nerves (which were severed), the results must have been caused by a contribution of the testes to the blood and then to the action of the added substance throughout the entire body.
In the November, 1962, issue of the journal Today’s Health, Donald G. Cooley, an American physiologist, published an article titled “Hormones: Your Body’s Chemical Rousers,” in which he reviewed the experiments of Bayliss and Starling and presented an updated, salient summary concerning the mechanism of hormone action. In May, 1979, scientists at the National Institute of Dental Research in Bethesda, Maryland, reported strong evidence that a virus can cause juvenile-onset, or type 1, diabetes. The most serious variety of the disease, type 1 diabetes is characterized by a lack of insulin. Ji-won Yoon, Marchall Austen, and Takashi Orodern isolated the virus, called Coxsackie B4, from the pancreas of a ten-year-old boy who died of a sudden and severe case of diabetes. The researchers grew the virus in cultures and injected it into mice. Some strains of the mice then developed diabetes. This evidence indicated that the Coxsackie virus can be a causal factor in some cases of diabetes. Nevertheless, the fact that not all of the mice developed the disease indicated that a genetic factor may be needed to trigger development of the disease.
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Grossman, Morton I. “Vitamins and Hormones.” In Advances in Research and Application, edited by Robert S. Harris. New York: Academic Press, 1958. Discusses vitamins and their sources, in addition to the discovery, distribution, and modes of action of the hormone secretin. Further addresses the fate of cholecystokinin produced by the duodenum. -
Henderson, John. A Life of Ernest Starling. New York: Oxford University Press, 2005. Biography covers Starling’s many contributions to medicine and addresses the passionate views he held, and voiced, on many other subjects, including education, Germany, and the British government. Includes illustrations, appendixes, bibliography, and index. -
Jenkin, Penelope. “Discovery of Hormones.” In Monographs of Pure and Applied Biology, edited by J. E. Harris. New York: Pergamon Press, 1962. A panoramic view of the salient experiments of Berthold, Starling, Kopec, and others. Discusses the mechanism of hormone action as well as the role of the central nervous system. -
Morgan, Howard E. “Endocrine Control Systems.” In Best and Taylor’s Physiological Basis of Medical Practice, edited by John R. Brobeck. 10th ed. Baltimore: Williams & Wilkins, 1980. An excellent reference text for students in the health professions. Discusses all aspects of hormonal control systems, including hormonal control of growth and protein metabolism. Hormonal control of permeability is well documented for ions, glucose, and amino acids. -
Schauf, Charles L., et al. Human Physiology: Foundations and Frontiers, edited by Deborah Allen. St. Louis, Mo.: Times Mirror/Mosby, 1990. A conceptual approach to a complex subject. Presents concepts systematically to demonstrate how organ systems interact with one another. Includes diagrams where required for clarification of the reciprocal fields of histology (the study of tissues) and physiology (the study of functions). -
Stille, Darlene R. “Science and Technology: Internal Medicine.” In Science Year: The World Book Science Annual, edited by Harrison Brown et al. Chicago: Scott & Fetzer, 1980. Includes Science File, a section that provides the “News of the Year” in about forty-five short articles alphabetically arranged by subject matter, from agriculture to zoology. The genetics section describes the research work of a team of scientists at City of Hope Medical Center who created a bacterial strain able to produce human insulin, a protein hormone used in treating diabetes.
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