GENERAL INTRODUCTION TO A DISCUSSION OF THE HORMONES E. M. K. GEILING. PI~ARMAMWGICAL LABORATORY, JOHNS H O ~ I NUNIVERSITY, S BALTIMORE, MD
It is proposed in this article, which is the first of a series to be printed in THISJOURNAL, to record briefly some general considerations concerning the glands of internal secretion, or ductless glands, and to describe some of the more important methods employed in the study of the functions of these organs. The discussion will he followed in subsequent issues by summarized statements, with occasional illustrations of the main facts, relating to our knowledge of the physiological functions of these so-called "regulators" within the animal organism. It is no exaggeration to say that research directed towards elucidating the manner of action and the chemical nature of hormones, as the products of secretion of these ductless glands are called, has met with quite unexpected success, and, although our knowledge of this phase of physiology is still meager, new facts, many of great practical value and scientific significance, are being brought to light almost daily. In fact, every branch of biology and medicine has workers in the field of endocrinology, who are obtaining information which is of considerable value in their respective spheres of scientific endeavor. It may be well a t the outset to point out the differencebetween a gland of external secretion and one of internal secretion. In the former, the product elaborated by the cells of the gland finds exit through a duct. For example, the secretion of the parotid gland, one of the salivary glands, leaves by way of Stenson's duct which opens into the mouth on the inside of the cheek. On the other hand, the active principle or hormone formed by the cells of a gland of internal secretion does not escape through a duct, hut is taken up directly by the blood stream and transported to different parts of the body, wherever i t may he needed. The pancreas is illustrative of both types, in that its cells form an internal as well as an external secretion. The latter is the pancreatic juice which escapes into the lumen of the small intestine through the pancreatic duct. The former is the now well-known insulin which is formed by the islets of Langerhans which constitute an integral part of the gland. This hormone, or chemical messenger, is taken directly by the blood stream and carried to all the tissues where i t plays an important role in the metabolism of the body carbohydrates. A deficiency of this hormone, brought about through disease of the islets of Langerhans, causes diabetes mellitus. Further discussion of this hormone or autacoid will follow later. As a result of the attention which within recent years has been focussed on the subject of endocrinology, practically every gland within the body has had supporters in favor of its being possessed of internal secretory
functions. In the present stage of our knowledge, however, i t would be rash to subscribe to this view. The most which can be said is that there is sufficient experimental or clinical proof to warrant classifying some of them as ductless glands, while in the case of others, the data are not as yet sufficiently convincing to justify them being looked upon as organs of internal secretion. Figures 1 and 2 are schematic charts showing the location in the body of the various organs belonging to the endocrine system. The pancreas, thyroid, p a r a t h y r o i d , pituitary body, suprarenals, the sex glands, the upper part of the duodenum, the liver, and the thymus are generally regarded as being the most important organs of internal secretion. In the case of the other structures shown in the charts there is still some uncertainty, though future investigations will no doubt show that a certain number of them a t least possess hormonal functions. The methods usually employed in determining the physiological functions of the ductless glands are essentiallylaboratory experimentation and clinical observations. Of laboratory procedures the following are usually adopted: 1. Partial or complete removal of the dand from an aniSCHEMATIC CHART OF E N D O C R I N E SYSTLM (,ither by operation or ...a..G.through destruction by chemical substances) and observation of the resulting structural, nutritional, and physiological alterations. 2. The whole gland or gland extracts, may be fed to or injected into a normal experimental animal and the changes thus brought about noted. 3. Animals from which a gland has been partly or completely removed may be fed with similar glands, or be injected with such gland extracts. Clinical methods include the observation of patients suffering from an increase or decrease in function of any particular gland, the study of
symptoms or signs occurring after surgical removal of a diseased gland; and the changes which take place following the administration of gland substance or glandular e x h c t s to such individuals. It is of importance to note, as has been emphasized by Dr. Abel in his recent Kober Lecture, that the mode of action of any given hormone on a tissue or organ depends to a great extent upon the chemical or functional state of the latter. For example, epinephrine when injected into an animal originally produces a rise of blood pressure, but, as Dale found, when an animal has previously been given an injection of ergotoxin, epinephrine c6 now causes a diametrically opposite response, in that there is a fall in blood pressure. In other words, the functional state of the body has been so altered by the previous injection of ergotoxin that the response to epinephrine has been completely Srsrrrrol, altered. Other similar instances D"-b=nucan be found in pharmacological literature. It follows as a necessary corollary to this view that while each member of the endocrine system ~;:::.p, when examined individually "'""" may be found to be possessed of one or more active principles which have striking physiological properties, such as raising I89 the blood pressure, causing the CHART OF ENDOCRINE SYSTEM uterus and other smooth mus- SWErIATlC *, cles to contract, lowering the blood sugar, or even causing structural alterations, its effect on the intact animal organism may be modified profoundly by the action of other glands. In short, the function of any particular gland must be viewed only as an integral part of a complex system in which each component exerts an influence upon the other members. At the moment this interrelationship of the glands of internal secretion is imperfectly understood but its importance is being more and more recognized. We are beginning to realize very clearly that either excess or diminished ".--&
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JANUARY, 1926
function of one gland is almost certain to influence the activity of several organs and as a result the sum total of disturbances produced in the body may often be far greater than would be expeded. Some of the changes produced are secondary to the improper function of the gland whose activity is interfered with by the derangement of a primarily diseased gland. While our knowledge of this aspect of the subject is admittedly rudimentary, there are a t present several striking instances where such an inter-relationship of the ductless glands exists. To cite but two examples: It has been known since remote antiquity that castration (depriving the body of the internal secretion of the testes besides rendering the subject sterile) causes striking alterations in the size and the structure of the hypophesis while the other internal organs are also altered. The outward expression of this internal glandular derangement is a striking alteration in the structure of the body. Some eunuchs may become abnormally tall; in others, growth may be stunted, while certain of them develop female characteristics, as far as the deposition of fat and configuration of the pelvis and breasts are concerned. The nature and extent of the changes produced vary with the age a t which the operation is performed. The personality of such individuals is also very considerably changed as a result of this operation and consequent upsetting of the regulatory system. Another illustration of the interdependence of the ductless glands is found in the case of the removal of the pituitary gland, which causes a marked atrophy of the ovaries. These examples, as well as others, give adequate support to the conception of the inter-relationship of the organs of internal secretion. It may be well to mention, too, that a t times this inter-relationship takes the form of an antagonistic action, such as where epinephrine and extracts of the posterior lobe of the pituitary body prevent insulin from lowering the blood sugar. This would indicate that one of the functions of the adrenals and the pituitary gland is to balance the internal secretory activity of the pancreas. We may thus look upon the normal functioning of the body (a very intricate and complex machine) as an expression of the coordinate activity of a number of internal secretory regulators, namely, the ductless glands which pour into the blood stream the active principles in such amounts as are necessary to maintain a balance of bodily activity. It should be remembered, however, that i t cannot be implied that hormonal regulation is the only one in the body, though certain authorities such as Sir Arthur Keith have gone as far as to ascribe the individual racial characteristics of every man, woman, and child to the varying amounts of hormones elaborated by the endocrine systems of their bodies. Due regard must also be paid to the roles of the nervous and other systems in the normal functioning of the human organism.
