HORMONES. Certain glands deliver their secretions on to a free surface by means of a definite orifice or duct. Two clear examples of this type are the mammary glands and the sweat glands. Others, however, have no duct, and the substances elabo rated by the activity of the gland cells are discharged not on to a free surface but into the blood stream. Such glands are known as the ductless glands or glands of internal secretion. The thy roid gland, the parathyroids, the suprarenal glands and the pitui tary gland are the most important examples of this type of endocrine organ.
In certain cases the two functions of producing an external and an internal secretion may be combined in the same gland. Thus the pancreas, in addition to delivering its external secretion the pancreatic juice into the duodenum via the pancreatic duct, also forms an internal secretion of great importance for the regulation of the sugar metabolism of the organism.
The substances produced by the activity of the cells of the ductless glands and discharged into the blood stream are charac terized by the property of serving as chemical messengers, pro duced in one organ and carried in the blood to another where their effect is manifested. They enable a chemical correlation of the activities of the organism to be brought about through the blood, pari passu with that which is the function of the nervous system. To substances of this nature Bayliss and Starling gave the name "Hormones," derived from the Greek bppAcw, "I arouse to activity." It seems clear that this chemical correlation is the more primi tive of the two methods by which co-ordination between different parts of the body is achieved. Starling has pointed out that in the lowest animals before the appearance of a central nervous system, it is by chemical means that co-adaptation of function is ensured. As examples he gives the movement of phagocytic cells toward an irritant, the chase for food and the approach of the gametes or sexual cells. In order that this relatively slow process may be applicable to a more complex organism, the development of a blood circulation is necessary, but before this occurs the need for quick responses has necessitated the setting aside of special reac tive cells—the rudiments of a central nervous system. That the two methods of correlation, chemical and nervous, are intimately connected will be clear from the detailed account of the various hormones.
The type of evidence which is relied upon in assigning endocrine function to a particular organ may now be considered. In the main the evidence is obtained by two methods, the one being the observation of changes resulting from the partial or complete re moval of the organ under consideration, either experimentally or by disease ; the other by observation of the effects produced by administration of various extracts of the gland. Information of the first kind dates from the 'introduction of castration probably as a religious rite ; that of the second type from the work of Schafer and Oliver in 1894.
Although a positive result under either or both of these heads does not constitute a rigid demonstration that a gland produces an internal secretion or hormone, much of the evidence on which several familiar organs are classed with the ductless glands is of this nature. As Hogben points out, to infer endocrine activity solely from the effects of removal of an organ "is hardly less un warranted than to deduce from the manifest consequences of de capitation that the head secretes a hormone that maintains the rhythmical contraction of the heart." Owing to the difficulty in demonstrating the presence in the blood of a hormone which may be of unknown chemical constitu tion and in minute amount, it is in certain cases necessary to rely on evidence of the type mentioned. The effects of removal of cer tain glands, or of injection of their extracts, are, however, so spe cific that, together with other indirect evidence, it is difficult to avoid the conclusion that their normal function is actually to elaborate, and discharge into the blood stream, a hormone which produces the specific effects observed.
Secretin.—The work of Bayliss and Starling in 1902 and 1903 on the regulation of the pancreatic secretion provides one of the best examples of the elucidation of the mode of action of a hormone. It had long been known, particularly from the work of Pawlow and his pupils, that the entry of the acid contents of the stomach into the upper part of the small intestine normally ini tiated the flow of pancreatic juice; and that the introduction of acid into the duodenum also induced pancreatic secretion. Bay liss and Starling showed that the results were still to be obtained when acid was introduced into a loop of gut completely separated from all nervous connections. The secretion of pancreatic juice could not therefore be due to nervous impulses ; injection of acid into the circulation itself did not activate the pancreas.
There remained theref ore the possibility that by the action of the acid on the cells lining the upper part of the gut a substance capable of exciting the pancreas to active secretion was liberated into the blood stream. This was tested experimentally and verified by Bayliss and Starling. The mucous membrane scraped from a strip of the upper end of the small intestine was ground with sand extracted with 0.4% hydrochloric acid and filtered. The fil tered extract injected into the circulation of a dog gave rise to a flow of pancreatic juice about one minute after the injection. To the active substance in the extract the name secretin was given, its precursor in the mucous membrane being called prosecretin.
Along with the secretin there was also in the extract a substance —termed a "depressor" substance—which brought about a fall in blood pressure following the injection. Bayliss and Starling demonstrated quite clearly that the pancreatic activity could be brought about equally satisfactorily with an extract which showed no depressor activity as a result of treatment with alcohol. The flow of pancreatic juice was not therefore a secondary effect due to the disturbance of the blood pressure.
Further, they demonstrated that secretin was a specific sub stance elaborated by the cells of the mucous membrane of the intestine; it was not to be found in extracts made from other tissues of the body.
The chemical structure of secretin is still unknown. Bayliss and Starling showed that the molecule of secretin was probably not large since it diffuses slightly through parchment paper, and found that it was easily destroyed by pancreatic juice and many metallic salts.
In 1926 J. Mellanby described a method for isolating secretin by absorbing the active substance by means of bile salts and sug gests that secretin is a polypeptide ; it is, however, not certain that secretin has yet been obtained free from impurity.
It must not be forgotten that pancreatic secretion can be brought about by nervous stimulation, and the question of the relative importance of the hormonic and nervous control of the pancreas remains to be decided. The different properties of the juice obtained by these two methods of stimulation suggests that in the intact animal both mechanisms are involved (see DIGES