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The Influence of the Internal Secretions on the Nervous System

  • E. Sharpey Schafer (a1)

The influence of the internal secretions is exerted by means of chemical substances—very few of which have been isolated or satisfactorily examined. Many of these substances closely resemble in their action that of medicaments, especially such drugs as the alkaloids. So far as their physiological action is concerned drugs can be classed in two divisions, viz., those which increase the excitability of irritable tissues, and incidentally induce their activity when quiescent; and those which diminish their excitability, and incidentally produce quiescence if administered during activity. As instances of the action of those two kinds of drugs on the nervous system strychnine and morphine may be mentioned; similar examples may be found in the action of antagonistic drugs upon the secreting glands, upon skeletal, plain, and cardiac muscle, and upon protoplasm in general. The principle is of extensive application, some drugs being definitely excitatory, others definitely inhibitory, the effect, whichever it may be, being produced by a reaction between the chemical substance which forms the active constituent of the drug and a constituent of the living tissue, this being in certain cases represented by a special material, termed by Langley “receptive substance,” which has in all probability been formed under the influence of the nerves which pass to the tissue. The action of the internal secretions is due to specific chemical substances which act upon or react with constituents of the cells. Such reaction, as in the case of drugs, tends either to increase or to diminish the excitability of particular tissues, either stimulating the living substance to activity or increasing its activity, or decreasing or arresting any activity that may be present. The expression “chemical messenger” was employed by Bayliss and Starling in their work on the action of secretin upon the pancreas to denote any material circulating in the blood which tends to excite a tissue to activity. Subsequently the word “hormone” was invented by Starling as a short equivalent—not, as he is careful to insist, to be confined to the chemical principles of the internal secretions, but to be used also for any chemical substance, of whatever nature or origin, which acts as an excitant; e.g., Starling gives as an example of a hormone the CO2 of the blood, which, when conveyed to the medulla oblongata, excites the activity of the nerve-cells composing the respiratory centre. Subsequent writers, e.g., Biedl, have displayed a tendency to restrict Starling's term to the active principles of the internal secretions, in place of using it, as he himself proposed, for all chemical substances exciting activity—a proposition in strict accordance with its derivation, which is from the Greek word μαω, I excite. This restriction of the term is the more unfortunate because it has become customary by most authors to include under the term of hormones or excitants substances which have exactly the opposite effect—that, namely, of restraining or inhibiting activity, the custom having arisen probably from the fact that at first the existence of such substances was not sufficiently recognised. Since it is obviously improper to apply the term “hormone” (or “excitant”) to inhibitory substances, I have ventured to propose that an analogous term, “chalone,” derived from the Greek word χαλω, I restrain, should be employed to designate such substances, and that a general expression denoting their drug-like character should be used to describe all the specific principles contained in the internal secretions which promote changes in other organs, whether in the way of excitation or inhibition. Such an expression is appropriately found in the term “autacoid,” which is derived from the Greek words oA, self, and kP, drug or remedy, i.e., a drug-like substance produced within the body itself: the latter part of the expression being already in general use in the form “panacea” or universal remedy. A striking example of a chalone or restraining principle is furnished by the ovary, which produces in its internal secretion a chemical substance—not as yet isolated—which restrains the development of the male characteristics in the female. When this restraint is lacking, as occurs after removal of the ovaries, a tendency to development of male characters makes its appearance. A hen, for example, deprived of its ovary develops the bodily form, the tail, comb and wattles of a cock, crows like the male bird, and even attempts to “tread” other hens. And if the ovary of another individual is successfully transplanted into such a bird, the chalone which is contained in its internal secretion inhibits the tendency to develop male characters, and these presently disappear, so that the animal again assumes all the characters of a hen. Nor is this occurrence of a chalone in the generative glands confined to the hen. There is one variety of Sebright fowls in which the cocks are hen-feathered. In this breed, as has been shown by T. H. Morgan, the testis contains cells, similar to certain cells in the ovary, which apparently yield a chalone, similar to that of the ovaries of ordinary breeds of fowl. And when the testes are removed from the hen-feathered Sebright cock, the castrated animal assumes the plumage characteristic of the ordinary cock-feathered variety of Sebright. Since, therefore, there are two principles of opposite character yielded by the internal secretions, I shall in speaking of their action upon the nervous system employ the expression “autacoid” as a general term to denote the active chemical agent of any secretion, and the special terms “hormone” and “chalone”—with their adjectives “hormonic” and “chalonic”—to express the mode of action of particular autacoids according to whether this is excitatory or inhibitory. These preliminary remarks are introduced to enable those members of my present audience who are not familiar with the history of the subject, and especially with its nomenclature, to understand exactly what is meant by the expressions I propose to use, in order to avoid the confusion which would otherwise result from the employment, as is so frequently done, of the same term—hormone—in opposite senses.

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(2) The thyroid is the only organ in the body which normally contains an appreciable amount of iodine.

(3) Murray has lately given the complete life-history of his first case, a woman, æt. 46, treated continuously and successfully with thyroid until her death at 74 {Brit. Med. Journ., 1920).

(4) Gley and Quinquaud state that the effect is not peculiar to extract of thyroid, but is produced by several other glandular extracts, and is less than that of liver extract.

(5) It must be stated, however, that Langley and others have failed to obtain this result with the phrenic.

(6) (6) Rogoff states that blood from the thyroid veins of dogs collected during massage of the organ and during stimulation of the cervical sympathetic does accelerate the metamorphosis of tadpoles. But the figures he gives of these hardly bear out this statement {Journ. Pharm, and Exper. Ther.t 1918, xii).

(7) Cannon and de Paz {Amer. Journ. Physiol., 1911, xxviii) have also got an increased extent and rate of contraction from the addition of serum. Such increase is generally followed by a period of rest, which they ascribe to inhibition caused by adrenalin in the blood. But a similar period of rest follows the increased contraction caused by thyroid extract alone, and the period of rest is evidently the physiological rebound from the previous period of over-activity

(8) The nervous symptoms of tetany are quite different from those of hyperthyroidism; in the latter there is no increase of galvanic excitability of the peripheral nerves and muscles such as is characteristic of tetany.

(1) An address given at the Annual Meeting of the Medico-Psychological Association, held in Edinburgh, July 20, 1922.

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The Influence of the Internal Secretions on the Nervous System

  • E. Sharpey Schafer (a1)
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