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The physiological studies by British physiologists William Maddock Bayliss and Ernest Henry Starling, at the beginning of the last century, demonstrated the existence of specific messenger molecules (hormones) circulating in the blood that regulate the organ function and physiological mechanisms. These findings led to the concept of endocrinology. The first 2 hormones were secretin, discovered in 1902, and gastrin, discovered in 1905. Both hormones that have been described are produced in the gut. This chapter summarizes the history around the discovery of these 2 hormones, which is perceived as the birth of endocrinology. It is noteworthy that after the discovery of these 2 gastrointestinal hormones, many other hormones were detected outside the gut, and thereafter gut hormones faded from both the clinical and scientific spotlight. Only recently, the clinical importance of the gut as the body's largest endocrine organ producing a large variety of hormones has been realized. Gastrointestinal hormones are essential regulators of metabolism, growth, development and behavior and are therefore the focus of a modern pediatric endocrinologist.

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This review describes the history of secretin discovery, identification, purification, and structural determination; cloning of secretin and its receptor; synthetic secretin; and highly specific and sensitive radioimmunoassay to define the characteristic physiological role on postprandial pancreatic fluid and bicarbonate secretion, which requires robust potentiation by cholecystokinin. Secretin plays a key role in the negative and positive regulatory mechanisms of exocrine pancreatic secretion. Secretin-releasing peptides were discovered in duodenal acid perfusates of both rat and dog and in canine pancreatic juice. The release and action of secretin and secretin-releasing peptides are in part mediated via vagovagal reflex mechanism involving afferent sensory neurons in proximal intestine and efferent cholinergic neurons in the pancreas. Besides acetylcholine, many neurotransmitters or neuromodulators influence release and action of secretin. The action of secretin in the pancreas depends on insulin, which also suppresses local release of somatostatin and pancreatic polypeptide. Thus, release and action of secretin are mediated via neurohormonal interaction. Clinical conditions with hypersecretinemia and hyposecretinemia are discussed. Synthetic human secretin is used for studies of exocrine pancreatic secretion, secretin-enhanced magnetic resonance cholangiopancreatography combined with exocrine pancreatic function test and diagnosis of gastrinoma syndrome. Therapeutic use of secretin is considered for the relief of severe pain in chronic pancreatitis.

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The pre-eminent achievements of the English physician and physiologist Ernest Henry Starling were his quantitative explanation of the transcapillary transport of fluid, the discovery of the first hormone, secretin, and his formulation of the law of the heart. In some ways Starling was an outsider and he was the centre of several scientific and social controversies. However, throughout his life he stressed fundamental scientific attitudes and ideas with remarkable persistence and power, although also balance, and his scientific achievements have stood the test of time.

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Secretin was discovered by Starling & Bayliss in 1902. Three years later the hormone concept and hormonal regulation were described and early regulatory physiology took a major step forward. After several years of unsuccessful investigations, secretin was isolated with new chromatographic techniques and subsequently synthesised in the 1960s. Radioimmunoassays in the 1970s confirmed the final endocrine role of secretin. Cloning and molecular hybridisation in the 1990s have identified the size of production, precursor, genetic structure, and evolutionary relation to other gastrointestinal peptides. In addition, the secretin receptor has been described. In recent years, synthetic secretin has been applied in the functional and structural diagnostics of pancreatic function and in experimental therapy. Although it was the first bioactive substance to be identified as a hormone, our knowledge of secretin today, 100 years on, is still incomplete.

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The establishment of a reliable radioimmunoassay for secretin in plasma enabled studies on the physiology of secretin. It was shown that secretin, i.e. the heptacosapeptide isolated by Jorpes and Mutt, is in fact responsible for the phenomena observed by Starling and Bayliss in 1902 when studying the stimulation of pancreatic bicarbonate secretion in response to duodenal acidification. Secretin is released in amounts considerably lower than anticipated, but these amounts are nevertheless sufficient to drive pancreatic and biliary secretion of bicarbonate. Whereas secretin in the fasting state is the most important stimulus to pancreatic secretion of water and bicarbonate, other hormones and nervous factors are essential for the majority of pancreatic postprandial secretion.

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The demonstration by Bayliss and Starling that acid liberates a chemical messenger from the cells of the duodenal and jejunal mucosa and that this, by traveling through the blood, excites the pancreas to secrete revolutionized physiology. It subsequently provided the impetus to establish endocrinology as a specialist field in medicine. Together, their contributions to physiology covered a vast sphere of knowledge, ranging from hormones to the heart and from enzymes to osmotic forces. Every subject that they studied was augmented by their efforts, and their lucid scientific writing brought both clarity and organization to the field of physiological endeavor throughout the world. Both contributed in a very definite way to crystallizing physiology into a rigorous scientific discipline and their respective texts the "Principles of General Physiology" (Bayliss) and the "Principles of Human Physiology" (Starling) established a framework of thought that for decades remained the lodestar of physiological science. As mentors, they devoted themselves to aspirant physiologists from all parts of the world, and their dedication to the activities of the Physiological Society in London was legendary. Indeed from 1896, when Starling became secretary, until the death of Bayliss in 1924, the two ran this august body in one capacity or another for more than a quarter of a century. There is little doubt that the felicitous collaboration that led to the discovery of secretin and the introduction of the concept of chemical messengers represents an advance that not only revolutionized physiological thought but the entire face of clinical medicine.

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The English physician E. H. Starling discovered in collaboration with the physiologist W. M. Bayliss secretin, the first hormone, in 1902. Three years later they introduced the hormone concept with recognition of chemical regulation, early regulatory physiology took a major step forward. The isolation and subsequent synthesis of secretin in the 1960s prepared the way for immunological techniques. Radioimmuno assays in the 1970s enabled demonstration of a direct endocrine role of secretin. Cloning and molecular hybridisation in the 1990s identified production site structure, precursor and evolutionary relation to other gastrointestinal peptides and to the secretin receptor. Although secretin was the first substance to be established as a hormone, even today our understanding is far from complete.

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Desde 1902, con la comunicación, ahora clásica, de la secretina, la gastroenterología y la endocrinología han permanecido íntimamente relacionadas. El desarrollo a través de los años, de técnicas de investigación morfológica y funcional, ha permitido conocer el origen y las secreciones de las células endocrinas de aparato digestivo y del sistema neuro-entérico. Se describe de manera cronológica el desarrollo del conocimiento en este apasionante campo de la gastroenterología endocrina

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