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The study of the glands of internal secretion, the endocrine glands, and the hormones which they synthesize and secrete. These glands are ductless; the hormones are secreted directly into the blood to be carried to the target tissue or organ. The hormones, or chemical messengers, are highly specific and their action may be selective or generalized. See Endocrine system (vertebrate), Hormone
the science concerned with the structure and function of the glands of internal secretion, or endocrine glands, the hormones manufactured by the glands, and the hormones’ manner of formation and effect on animals and man. Clinical endocrinology studies the diseases that result from functional impairment of the endocrine glands.
Endocrinology is related to many branches of biology, medicine, and veterinary science; it has particularly close ties to physiology, from which it evolved as an independent science, as well as to biochemistry, pharmacology, and molecular biology. On the basis of the progress made in understanding how the hormones activate the genes, endocrinology may be defined as the science concerned with the regulation of the basic functions of the organism. The modern subspecialty neuroendocrinology studies the interaction of the nervous system and endocrine glands in regulating body functions.
Historical sketch. The castration of farm animals has been practiced since ancient times. Men, too, were castrated—for example, the Eastern slaves who served in the harems as eunuchs and the members of certain religious sects, such as the Skoptsy in prerevolutionary Russia. In all such cases, distinct changes were observed not only in sexual function but throughout the body—in growth, muscular development, and activity of the nervous system. As early as the 16th to 18th centuries, almost all the organs now known as the glands of internal secretion had been described by many anatomists together with the other organs of animals and man, although the endocrine glands’ function was unknown at the time. The concept of an organ or gland with internal secretion was formulated in 1830 by the German physiologist and naturalist J. P. Müller.
Endocrinology evolved into a scientific discipline in the 19th century, when certain diseases resulting from injury to some of the endocrine glands were described. For example, thyroid disease was described by the Irish scientist R. Graves in 1835 and by the German scientist K. von Basedow in 1840; in 1855 the English physician T. Addison described adrenal disease in man. The Swiss surgeons T. Kocher and J. L. Reverdin studied endemic goiter (1882–83) and scientifically justified its treatment by surgery.
The earliest experiments in endocrinology were performed by the German physiologist A. Berthold, who in 1849 showed that transplanting the testes under the skin or in the abdominal cavity of young castrated roosters prevents the development of such phenomena as are observed after castration. Several years later, in 1855, the French physiologist C. Bernard introduced the concept of internal secretion.
The endocrine glands attracted even greater interest after the studies carried out by the French scientist C. Brown-Séquard (1889) proved, in his opinion, that testicular extracts have a rejuvenating effect on the aging organism. It was at this time that extensive research studies making use of animals were initiated in clinical and experimental endocrinology. In 1889 the German scientists J. von Mering and O. Minkowsky showed that removal of the pancreas in animals causes diabetes mellitus. In 1901 the Russian scientist L. V. Sobolev made an important contribution by showing that diabetes mellitus is related to loss of the function of internal secretion in the islet tissue of the pancreas. He also pointed out the possibility of treating diabetes with a preparation derived from the pancreas.
The functional changes resulting from removal of or injury to the endocrine glands suggested that some especially active compounds may be manufactured by the glands. For a long time, however, efforts to isolate such compounds were unsuccessful. It was not until 1901 that adrenaline, the hormone produced by the adrenal medulla, was first isolated in crystalline form by the American scientist T. Aldrich and the Japanese scientist J. Takamine, and not until 1905 that it was synthesized by the German scientist F. Stolz and the English scientist H. Dakin. At the same time (1905) the English physiologist E. H. Starling introduced the term “hormone.”
The thyroid hormone thyroxine was isolated in 1915 by the American scientist E. Kendall, and its chemical structure was established in 1926 by the English scientist C. Harington. In 1921–22, insulin was isolated from the pancreas by the Canadians F. Banting and C. Best, and somewhat later the hormone glucagon was found in the gland. Studies by the German scientists F. Smith, B. Zondek, and S. Aschheim on the hormones of the anterior pituitary gland date back to the same period, although the hormones themselves were not isolated in pure form until the 1940’s.
Various compounds were isolated in the late 1920’s and early 1930’s—specifically, the estrogen compounds isolated from the follicular fluid by the American scientists E. Allen and E. Doisy, the German scientist A. Butenandt, and the Englishman H. Marian (1924–29); the hormone progesterone, isolated from the corpus luteum by Allen and Butenandt in 1934; and the corticosteroids, such as hydrocortisone, cortisone, and corticosterone, isolated from the adrenal cortex by the Swiss T. Reichstein and the American E. Kendall. Aldosterone was isolated from the adrenal glands in 1953 by an Anglo-Swiss research team headed by S. Simpson and J. Tait.
The isolation of hormones in their pure form and the establishment of their structure made it possible to obtain many hormones by chemical means, to study their effect on the organism, and to determine more precisely the role of each gland. As a result of such research, it was established that the endocrine glands function as part of a unified interrelated system rather than separately. The hypophysis cerebri, or pituitary gland, was found to be part of a single functional complex with the hypothalamus. Studies by the English scientist H. Harris (1952), by the Americans S. McCann and A. Schally, and by the French physiologist R. Guillemin showed that the medial portion of the hypothalamus secretes various biologically active substances—known as releasing hormones—which are carried through the blood vessels to the anterior part of the pituitary gland, where they stimulate the synthesis and release of the hypophyseal hormones.
In the second half of the 20th century, much has been learned about how hormones work. It has been determined that the steroid hormones act at the deoxyribonucleic acid level, stimulating the corresponding genes; this results in the synthesis of the essential enzymes or other specific proteins that affect metabolism. The proteo hormones do not penetrate into the cell; they act on the internal cell membrane, which contains the enzyme adenyl cyclase. The latter converts adenosinetriphosphoric acid (ATP) to cyclic adenosine monophosphate, which interacts with and activates various intracellular enzymes (protein kinases) and through them affects the nuclear apparatus of the cell.
The activity of an endocrine gland depends on the degree of concentration of its hormone (or hormones) in the blood. For example, an excess of thyroid or adrenocortical hormones reduces the secretion of hypothalamic releasing hormones, which in turn diminishes the secretion of hypophyseal hormones and lowers the thyroxine or corticosteroid levels in the blood. The Soviet biologist M. M. Zavadovskii regarded this long-known mechanism as the basic principle of humoral interrelation and called it the “plus-minus interaction”—a particular case of the general law governing the maintenance of hormonal balance in the body. This principle of interaction was subsequently called feedback.
Such interactions in the endocrine system are effected both by the action of certain glands’ hormones on other glands and by neural mechanisms; they occur not only in the hypothalamus but also at lower levels of integration. As early as 1910, M. N. Cheboksarov showed that the adrenal glands’ medullary secretion is regulated by the nervous system. I. P. Pavlov and his students noted the influence of higher nervous activity on the endocrine system.
Clinical endocrinology. As a branch of clinical medicine, clinical endocrinology studies diseases of the endocrine system—their epidemiology, etiology, pathogenesis, symptoms, treatment, and prevention—as well as the changes that take place in the endocrine glands in the presence of other diseases.
Modern research methods can reveal the causes of many endocrine disorders, such as bacterial disorders (for example, tuberculosis of the adrenal cortex with progressive functional insufficiency) and endocrine gland diseases of the viral, traumatic, and vascular type. Psychogenic and hereditary factors are also important. It is often difficult to distinguish between the factors that are the principal causes of an endocrine disease and the conditions contributing to the evolution of the disease from its preclinical stages into its latent and overt stages (for example, negative psychic influences in diabetes mellitus). The causes of endocrine diseases frequently remain unknown.
Current notions about the pathogenesis of endocrine diseases are based on the study of morphological changes in the corresponding glands and of the glands’ functional condition as well as the condition of the systems that regulate glandular activity. Diseases that affect the glands’ function—namely, those characterized by increased glandular activity (hyperfunction) or decreased activity (hypofunction)—are distinguished from those in which hormonal secretion remains within normal physiological limits. The various stages that mark the course of endocrine diseases are (1) the preclinical, or earliest, stage, which can be diagnosed only from indirect symptoms, (2) the latent stage, detected by means of special diagnostic tests, and (3) the overt stage, with typical manifestations. Thus, for example, diabetes mellitus in its preclinical stage is presumed to exist at birth in the case of a large fetus both of whose parents are diabetic; the latent stage is diagnosed by means of a glucose tolerance test.
The treatment of endocrine diseases is based on the principle of maintaining the hormonal regulation of functions with physiological limits. Usually, in the absence of complications, diseases marked by glandular hyperfunction can be successfully treated by means of chemical agents that selectively reduce excessive glandular activity, X-ray irradiation, the use of radioactive isotopes that damage the hormone producing cells, or surgery. In the case of diseases marked by hypofunction, normal hormonal levels are achieved by means of hormonal preparations (such treatment being known as replacement therapy, as in the treatment of diabetes mellitus with insulin) or preparations that stimulate the corresponding glands. Identification of the “risk factors”—that is, conditions that favor the development of a disease—is very important. In diabetes mellitus, for example, such factors include hereditary predisposition to the disease and obesity.
In the USSR, clinical endocrinology is taught in the departments of internal medicine and departments of endocrinology of medical schools and institutes of advanced medical training. In the other socialist countries, too, institutes of advanced medical training include departments of endocrinology.
Practical significance. Modern chemical and physicochemical methods make it possible to detect the presence of hormones not only in the endocrine glands, where they are usually found in abundance, but also in the blood and urine, where they are present in minute quantities. Thus certain hypotheses may be formulated about the manner in which hormones are synthesized and converted within the organism. The advances made in endocrinology led to advances in the related branches of medicine, and particularly in clinical endocrinology. The identification of hormones and of the products of their conversion resulted in more accurate clinical diagnoses of various endocrine diseases. At the same time, the availability of pure hormones and hormonal preparations made it possible for these diseases to be successfully treated. Many hormonal preparations have proved effective in the treatment of collagen diseases, bronchial asthma, cancer of the mammary gland and prostate, and some diseases of the kidneys, liver, and other organs.
The findings of endocrinology are being successfully applied in veterinary medicine. In addition to the ancient practice of castration as a means of altering the behavior of farm animals and fattening them, livestock breeders are developing other endocrine methods designed to influence fattening and fertility. Methods have been devised for hormonal stimulation of multiple births and hormonal regulation of the sexual cycle in farm animals. Extensive research is under way on the use of a new class of hormonal substances—the prostaglandins. Hormonal stimulation of the sex glands is an important factor in modern fish breeding. For example, the gonadotropic hormone of the pituitary gland is used in preparing the fish for spawning—a procedure worked out by the Soviet scientist N. A. Gerbil’skii.
Throughout the world, intensive efforts are devoted to the study of hormones and their action, especially at the molecular level. Modern endocrinology is chiefly concerned with the hormonal regulation of such functions as metabolism and with the origin, early diagnosis, treatment, and prevention of diabetes mellitus and other endocrine disorders.
Scientific institutions, organizations and periodicals. In the USSR, research studies in endocrinology are carried out at the I. P. Pavlov Institute of Physiology of the Academy of Sciences of the USSR (Leningrad), the Institute of Experimental Endocrinology and Hormone Chemistry of the Academy of Medical Sciences of the USSR (Moscow), the Kiev Institute of Endocrinology and Metabolism, the Ukrainian Institute of Experimental Endocrinology and Hormone Chemistry (Kharkov), and at various other institutes, medical school clinics, and institutes of advanced medical training. Analogous research systems operate in the other socialist countries as well. In the capitalist countries, aspects of clinical endocrinology are studied in the laboratories and clinics of universities, hospitals, and specialized research institutes.
National societies of endocrinologists and of diabetes specialists exist in almost all the developed countries. There are also international societies of endocrinologists and diabetes specialists. In 1975 the All-Union Scientific Society of Endocrinologists (founded 1947) joined the International Association of Endocrinologists (founded 1960). International congresses of endocrinologists are held every four years; the first was held in Copenhagen in 1960. In addition, international congresses are held on specific problems in endocrinology—for example, on diabetes mellitus and the role of steroid hormones.
Research results are published in various biological and medical journals, both general and specialized; such journals include, in the USSR, Problemy endokrinologii i gormonoterapii (published since 1955); in the United States, Endocrinology (Philadelphia, since 1917), Diabetes (New York, since 1952), Prostaglandins (Los Altos, since 1972), Steroids (San Francisco, since 1963), and The Journal of Clinical Endocrinology and Metabolism (Springfield, since 1941); in France, Annales d’Endocrinologie (Paris, since 1939); in Great Britain, The Journal of Endocrinology (Cambridge, since 1939); in Denmark, Acta endocrinologica (Copenhagen, since 1948); in the Socialist Republic of Rumania, Endocrinologia (Bucharest, since 1956); in Italy, Acta diabetolo-gica latina (Milan, since 1964); in the German Democratic Republic, Endokrinologie (Leipzig, since 1928); in the Czechoslovak Socialist Republic, Endocrinologia experimentalis (Bratislava, since 1967); and in the Federal Republic of Germany, Hormone and Metabolic Research (Stuttgart, since 1969).
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Rossiiskii, D. M. “Istoriia endokrinologii.” In V. D. Shervinskii and G. P. Sakharov, O snovy endokrinologii. Leningrad, 1929.
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Textbook of Endocrinology, 5th ed. Edited by R. H. Williams. Philadelphia, 1974.
N. A. IUDAEV and V. G. BARANOV