Functions of The Endocrine Glands

Functions of the Endocrine Glands

These Vital Organs and TheirSecretions are discussed by

Robert A. Stevenson, D. D. S., R. Ph.

Dental Therapy Editor

 

                There are an increasing number of investigators who are of the opinion that the activity of the endocrine glands have a decided influence on dental health, the fact that one or more of these ductless glands is one of the controlling factors in blood calcium, alone should make them worthy of our consideration.

It is far beyond the writer’s limited knowledge to present this subject in its entirely and so will only attempt to present a few of the better known facts. As McQuarrie said in a recent article appearing in the May issue of The Journal Lancet; “at the present time new discoveries in this important field are being reported in the biological, medical and clinical literature at so great a rate that no single investigator can possibly keep himself completely informed on every phase of the subject.”

Lorand said in Old Age Deferred, “The condition of the sexual glands and the thyroid gland also powerfully influence the condition of the teeth which can be seen plainly by the fact that all the alterations of these glands as in pregnancy, in chronic conditions, etc., may produce important changes in the condition of the teeth and the alveolar processes, in some cases we were able to improve swelling and hyperemia conditions of the gums by the administration of thyroid extract.”

The term “internal secretion “ is used to designate those secretions of glandular tissues which, instead of being carried off to the exterior by a duct, are eliminated in the blood or lymph. The term, however, seems to have been employed first by Claude Bernard, who emphasized the distinction between the ordinary secretions, or external secretions, and this group of internal secretions. Experience has shown that not only the ductless glands, but some at least of the typical glands provided with ducts may give rise to internal secretions, the pancreas, for example.

They yield internal secretions of one kind or another and modern investigations have demonstrated that there is a complicated interrelation among the secretions as regards their section on body metabolism. The conception that certain glandular organs may give rise to chemical products which on entering the circulation influence the activity of one or more other organs has found a fruitful application in the study of the digestive secretions. The gastric and pancreatic secretions may be regarded as examples of internal secretions. Chemical products of this kind which stimulate the activity of other organs Starling designates as hormones.

It is usually assumed that each ductless gland secretes or may secrete a specific hormone which is given to the blood or lymph and severs to influence in some definite way the functional activity of distant tissues. The hormones differ from the enzymes which characterize the external secretion both in their chemical nature and their mode of action. They are not proteins and they act not as catalyzers, but as direct chemical reagents after the manner of alkaloids and similar organic drugs.

Schafer calls attention to the fact that some hormones inhibit functional activity while others act as a chemical stimulant. The term “hormone” (hormao, I excite), etymologically considered, is not applicable to the former class. He suggests, therefore, the general term “autocoid substances” (acos, a remedy), and subdivides them into two groups according as they stimulate or inhibit.

Hormones—stimulating action

Autocoid substances

Chalones—inhibitory action

 

THE THYROID AND PARATHYROID AND PARATHYROID GLANDS—The most important and definite outcome of the work on internal secretions has been obtained with the thyroid tissues. The progress of this work has made it evident that a distinction must be made between the thyroid gland and the parathyroid bodies. The thyroid gland consists of two elongated oval lobes, lying one on either side of the trachea where it joins the larynx and about 5 to 6 cm. long.

The parathyroids are very small bodies, four in number, each about 6 to 7 mms. Long, lying on the posterior face of the thyroid lobes, two to each lobe.

EFFECT OF REMOVAL OF THE THYROIDS—If the parathyroids are not injured removal of the thyroids in the adult animal does not cause death, but brings about certain marked and characteristic changes in metabolism. The oxidations of the body, as indicated by the basal metabolism, are greatly diminished, sometimes by as much as 40 percent, and the final result is a condition of general malnutrition affecting most of the tissues. Ossification is delayed and the bones fail to reach their normal length, so that the animals are under-sized and poorly developed. It has been found that the ill-effects of thyroidectomy may be obviated by grafting thyroid tissue in other parts of the body, by injecting thyroid extracts subcutaneously or more simply still by feeding thyroid tissue to the animal.

EFFECTS OF INJECTING OR FEEDING THYROID TISSUE—When thyroid tissue or extract is administered by injection or by feeding there is a marked increase in the body metabolism. Basal metabolism is raised and there is an increased elimination of nitrogen. The body loses in weight, and in human beings various characteristics symptoms develop, such as a rapid heart-beat, nervous excitability, flushing, etc.

THE THRYOID HORMONE—THYROXINE—From the statements made above it is evident that the thyroid contains a material which has a powerful stimulating effect on body metabolism, and we may infer, on the basis of the results of thyroidectomy, that this material is supplied constantly to the body in the internal secretion of the gland. The nature of this principle or hormone has been determined. Baumann in 1896 isolated a substance from the colloid material which he designated as iodothyrin. It gave the same physiological reactions as thyroid tissue or extracts and was characterized by its large content of iodine, 9.3 percent of the dry weight. In 1914 Kendall succeeded in isolating a crystalline body to which he gave the name thyroxine and the empirical formula C12H10O3NI3. It gives the same physiological and therapeutic effects as thyroid extracts. In 1926 Harrington suggested a modification of Kendall’s method of isolating this substance which gives a larger yield.

THYROXINE HAS MARKED EFFECTS UPON METABOLISM—As little as 1milligram given to an adult will cause an increase of 2 percent, in the basal metabolism. When injected into man the physiological effects develop slowly during a number of days. The striking peculiarity of thyroxine  is its content of iodine. We may assume that the specific action of the thyroxine is dependent in some way upon the presence of iodine in its molecule. Feeding iodides to the animal may increase the amount by several hundred percent, and observations reported by Seidell and Fenger indicate of the year, the maximum occurring in the summer and early autumn. The significance of the Iodine is emphasized by its relation to pathological conditions inman which are referred to below. The general conclusion to be drawn from the known facts is that thyroxine is formed constantly in the glands and is distributed to the other tissues through the blood. Its action is to stimulate and regulate the metabolism of the body.

Cretinism is due to congenital atrophy or fibrous degeneration of the thyroid in young children. In cretins there is a marked retardation of growth, the sex glands retain an infantile condition, the epocermal tissues show a defective development and the central nervous system is arrested in its growth, giving a condition of idiocy or feeble-mindedness. These conditions may be alleviated or removed by the use of thyroid extracts, or the cretinism may be prevented by providing the mother with sufficient iodine-containing food during pregnancy.

In the condition known as Graves’ disease, in ophthalmic goiter, there is supposed to be anover-activity of the thyroid.  In these cases the skin is lax and moist, the metabolism is greatly increased, there is a characteristic protrusion of the eyeballs (exophthalmos), nervousness, a rapid heart-beat, and increased blood-pressure. The treatment for such cases takes the form of surgical removal of part of the gland.

Tetany Results from Removal of Parathyroids

Earlier observers had not made this distinction and in the surgical or experimental removal of the thyroids had excised also the parathyroids. This tetany exhibits itself as fibrillar contractions of the muscles, a general muscular tremor, tonic and clonic spasms of the muscles or “intention spasms,” that is, spasmic or uncoordinated contractions following upon an effort to make a voluntary movement. Macallum and Voeglin find that injection or ingestion of solutions of calcium salts removes completely the symptoms of tetany as the result of unintentional removal of the parathyroids during the course of a surgical operation on the thyroid bodies. In addition to the tetany parathyroidectomized animals show a characteristic increase in the irritability of the peripheral nerves and muscles to galvanic stimulation. Removal of the parathyroids in dogs is followed death in a few (one to four) days with the development of tetany and a falling of the calcium content of the blood. Tetany appears when the concentration of calcium drops to about 7 mgms, per 100 c.c. of blood. It would seem that the regulation of the concentration of calcium like the regulation of the concentration of sugar requires the activity of a specific hormone. How it sets remains unknown.

THYMUS—The physiology of the thymus gland is very obscure, in fact, nothing that is definite can be said about its functions, except perhaps that the gland is concerned in some way with the processes of growth in the young animal. Park and McClure, as also Tongu, report that complete thymectomy is certainly not followed by the death of the animal, and that, therefore, whatever functions it fulfills are not essential to the life of the organism. Moreover, they could detect no effect upon the growth of the bones or of the body in general.

ADRENAL  BODIES—The adrenal bodies—or, as they are frequently called in human anatomy, the suprarenal capsules—belong to the group of ductless glands. It was shown first by Brown-Sequard (1856) that removal of these bodies is followed rapidly by death. The symptoms preceding death are great prostration, muscular weakness, and marked diminution in vascular tone. These symptoms resemble those occurring in Addison’s disease in man—a disease which clinical evidence has shown to be associated with pathological lesions in the suprarenal capsules. It has been proposed to speak of the cortical tissue as the interrenal gland and of the medulla as the suprarenal or the chromaffin or chromaphil gland, but for our purpose it will be simper to state briefly the main facts that have been obtained under the headings cortex and medulla.

THE MEDULLA—THE ACTIVE PRINCIPLE, EPINEPHRINE—Chemical investigations of the substance in the medulla which causes the inhibition of the heart and the rise of blood-pressure have been very successful. The substance has been prepared in pure form, its chemical structure is known, and it has been made synthetically outside the body. This active substance is designated in the literature under a variety of names, those commonly used being epinephrine, adrenaline, and adrenine.

PHYSIOLOGICAL ACTION OF THE EPINEPHRINE—As stated, above, solutions of epinephrine give a marked effect upon the heart-rate and blood pressure. The great slowing of the heart-rate is due either to a direct action of the epinephrine on the cardio-inhibitory center, or, as seems more probable, is caused by a reflex effect on this center, resulting from the stimulating action of the hypertension upon the afferent fibres in the arteries. It disappears when the vagi are cut or after the administration of atropine. It seems probable that this effect is due to a stimulating action upon the endings of the accelerator nerve in the heart. The addition to the heart effect epinephrine causes a strong contraction of the arterioles in certain areas,  and experiments demonstrate that this effect is due mainly to a peripheral action it is this action that produces the great rise in blood-pressure, seen especially after the antagonistic influence of the cardio-inhibitory center is thrown out by section of the vagi. Under usual conditions this effect on blood pressure is short lasting. The arterial pressure after reaching a maximum falls off rapidly to normal, but a new rise can be produced by a new injection.

THE CORTICAL TISSUE—Most observers agree that the cortex does not contain epinephrine. The nature of the secretion furnished by the cortex and its normal functional value are matters of speculation only at present.

Observers have also called attention repeatedly to the fact that the cortex has some relation to the activity of the sexual glands. During pregnancy the cortex undergoes hypertrophy, and in some cases pathological changes affecting the cortex alone have been followed by precocious development of the sexual organs.

PITUATARY BODY (Hypophysis)—This body is usually described as consisting of two parts—a large anterior lobe of distinct glandular structure and a much smaller posterior lobe of nervous origin and composed chiefly of neuroglia cells and fibers.

EXTRACTS OF THE POSTERIOR LOBE—Since the posterior lobe consists of the pars nervosa and the pars intermeia its extracts will contain material from both structures. It has not been possible to determine whether one or both parts furnish the active substance obtained.

  1. The blood-pressure is raised and the heart-rate is slowed.
  2. There is an increased secretion of urine, the diuretic effect.
  3. The extracts cause a contraction of the plain muscle of the uterus.
  4. In a lactating animal there is an increased flow of milk.

The commercial preparations of the gland which have appeared under different names, pituitrin, hypophysin, etc., exhibit all three activities to some degree.

EXTRACTS OF THE ANTERIOR LOBE—Extracts of the anterior lobe when injected cause no immediate result, but experiments made upon different animals from the protozoa to the mammal indicate that they have affect the processes of growth in the direction of an acceleration. Evans and Long have shown that the intraperitoneal injectionof extracts of the anterior lobe of the bovine hypophysis into rats is followed by distinct effects on growth. The animals developed beyond the normal size, the growth curves exhibiting a postpubertal acceleration which affected not only the size and weight of the animal as a whole, but was evident in the skeleton and the visceral organs with the exception of the reproductive tract.

REMOVAL OF THE PITUATARY BODY—Very contradictory reports are made upon the effect of complete removal of the hypophysis. Some observers state that death occurs in a short time, while others find that the animal survives without distinctive symptoms.

THE FUNCTIONS OF THE HYPOPHYSIS—It is difficult to construct from the experimental results briefly summarized in the preceding pages any definite views in regard to the precise functions of the hypophysis. It seems clear that the anterior and posterior lobes have entirely different and possibly quite independent functions. The relations of the anterior lobe to body growth are beyond question, but the way in which its secretion acts upon body metabolism is not known, and the special case of its effect upon the growth of the adrenal cortex and the thyroid body offers a problem of great complexity.

THE PINEAL BODY (Epiphysis Cerebri)—This small body projects from the roof of the third ventricle and embryologically develops as an outgrowth from this vessel of the brain. In early life it has a glandular structure which seems to reach its greatest development at about the seventh year. After this period and particularly after puberty it undergoes a process of involution during which the glandular structure gradually disappears and its place is taken by fibrous tissue. The gland is noteworthy also for the appearance of calcareous concretions, the so-called brain sand, which may appear even in early life. Intravenous injections of extracts of this gland seem to cause a distinct fall in blood-pressure, indicating the presence of the depressor substance.

ORGANS OF REPRODUCTION—That the reproductive glands have an internal secretion seems to be demonstrated by the effect of castration in modifying the subsequent development of sex characteristics. The castrated animals develop into a neutral type which in the bird approaches that of the normal male, but in the mammals resembles rather the appearance of the female. Since this effect of castration is not obtained when a reproductive gland has been previously grafted in some other region of the body, we may infer that an internal secretion is given to the blood which normally controls the development of the so-called secondary sex characteristics.

PANCREAS—The importance of the external secretion, the pancreatic juice, of the pancreas has long been recognized, but it was not until 1889 that von Mering and Minkowski proved that it furnished also an equally important internal secretion. These observers succeeded in extirpating the entire pancreas without causing the immediate death of the animal, and found that in all cases this operation was followed by the appearance of sugar in the urine in considerable quantities.

It is believed that the pancreas forms an internal secretion which passes into the blood and plays an important, indeed, an essential part in the metabolism of sugar in the body. Evidence has accumulated to show that the tissue concerned in this important function is not the pancreatic tissue proper, but that composing the so-called island of Langerhans. In men these islands are scattered through the pancreas, forming spherical or oval bodies that may reach a diameter of as much as one millimeter.

Pancreas has Two Functions

According to Sebolow ligation of the pancreatic duct is followed by a complete atrophy of the pancreatic cells proper, while those of the islands of Langerhans are not affected. Since under these conditions no glycosuria occurs while removal of the whole organ including the islands is followed by pancreatic diabetes, the obvious conclusion is that the diabetes is due to the loss of the islands. This conclusion is strengthened by reports from the pathological side. A number of observers (Opie, Sebolow, Herzog, et al) find that in diabetes mellitus in man the islands may be markedly affected. They show signs of hyaline degeneration or atrophy, or in severe cases may be absent altogether. The general belief, therefore, is that these cells furnish an internal secretion which is essential in some way in the sugar-metabolism of the body. When the secretion is deficient or absent, diabetes develops.

INSULIN—Use of these extracts in the laboratory upon diabetic (depancreatized) dogs and in medical practice upon diabetic patients had demonstrated that they are effective in removing all usual symptoms of diabetes, namely, the hyperglycemia, the glycosuria and the acetonuria, besides bringing about a marked improvement in the general physical and mental condition of the individual. The methods used for obtaining insulin from the pancreas for therapeutic purposes have been modified by different workers.

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BIBLIOGRAPHY

                The Journal Lancet—May issue—Lancet Publishing Co., Minneapolis, Minn.

Old Age Deferred—By Arnold Lorand, M.D., Carlsbad, Austria. Published by F.A. Davis Company, Philadelphia, 1911.

A Text-Book of Physiology—By William H. Howell, Ph.D., M.D., Sc.D., L.L.D. Published by W.B. Saunders Company, Philadelphia and London, 1930.

June 19, 1936