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Gladstone RJ. and Wakeley C. The Pineal Organ. (1940) Bailliere, Tindall & Cox, London. PDF

   The Pineal Organ (1940): 1 Introduction | 2 Historical Sketch | 3 Types of Vertebrate and Invertebrate Eyes | Eyes of Invertebrates: 4 Coelenterates | 5 Flat worms | 6 Round worms | 7 Rotifers | 8 Molluscoida | 9 Echinoderms | 10 Annulata | 11 Arthropods | 12 Molluscs | 13 Eyes of Types which are intermediate between Vertebrates and Invertebrates | 14 Hemichorda | 15 Urochorda | 16 Cephalochorda | The Pineal System of Vertebrates: 17 Cyclostomes | 18 Fishes | 19 Amphibians | 20 Reptiles | 21 Birds | 22 Mammals | 23 Geological Evidence of Median Eyes in Vertebrates and Invertebrates | 24 Relation of the Median to the Lateral Eyes | The Human Pineal Organ : 25 Development and Histogenesis | 26 Structure of the Adult Organ | 27 Position and Anatomical Relations of the Adult Pineal Organ | 28 Function of the Pineal Body | 29 Pathology of Pineal Tumours | 30 Symptomatology and Diagnosis of Pineal Tumours | 31 Treatment, including the Surgical Approach to the Pineal Organ, and its Removal: Operative Technique | 32 Clinical Cases | 33 General Conclusions | Glossary | Bibliography
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The Pineal Organ - The Human Pineal Organ

Chapter 28 The Functions of the Pineal Body

We do not propose to deal at length with the controversial question of the function of the mammalian pineal organ, which has been very fully discussed in publications specially concerned with the endocrine glands ; nor do we propose in this section to discuss the various functions attributed to the pineal organs of fishes, amphibia, and reptiles, which we have already alluded to (pp. 6, 46, 230) ; but from the practical standpoint of whether the use of pineal extracts as a therapeutic measure should be continued or should be discontinued, we believe that the present time is ripe for a short review of the principal results which have been obtained from recent experimental work on the function of the pineal gland in birds and mammals.

The evidence which is often contradictory may be classified under two principal headings, namely :

A — The results of experimental work on animals. B — Observations on the human subject.

A. Experimental Work on Animals. — The biochemical aspect of this subject has been fully dealt with in numerous articles in the physiological and pharmaceutical journals and is beyond the scope of the present treatise ; we shall therefore limit our description to the consideration of the general results of experimental work under the following categories :

1. The results of pinealectomy.

2. The effects of feeding with pineal substance and injection of

pineal extracts.

3. The influence of pineal grafts.

In the consideration of each of these subdivisions we shall allude first to results which are deemed to be of a positive character and afterwards to those which are negative. We shall also limit ourselves to a brief discussion on the more important and typical results which have been obtained by authoritative workers, and we shall not attempt to make a complete record of the numerous papers of an indecisive nature which have been published on this subject, references to which will be found in the larger monographs dealing with the organs of internal secretion and the principal journals on endocrinology.

421


422


THE PINEAL ORGAN


Pinealectomy

Assuming that the pineal organ exerts an inhibitory influence on body growth and the development of the sexual organs, perhaps the most striking positive results which have been obtained in support of this view were those described by Foa in 19 12 and Izawa in 1922. Foa performed the difficult operation of removing the pineal gland in young chicks between the ages of 5 and 7 weeks. The mortality was large and only a small number of chicks survived. After a period of 3 months the latter showed that the general development of the body had been much more rapid in the experimental birds than in the controls, and also



Fig. 282. — A — Crest, and B — Testicle of a Cock from which the Epiphysis had been removed three months previously ; a — crest, and b — testicle of a Normal Control Specimen of the Same Age.

The development of the experimental animals was much more rapid than the controls, and the development of the secondary sexual characters (crow, crest, spurs) was equally precocious.

(After Foa ; redrawn from UEpiphyse, J. Calvet.)

that the development of the secondary sexual characters had been more precocious and active in the experimental animals, namely, the growth of the comb and spurs and the early occurrence of crowing (Fig. 282). Moreover, at the age of 10 to 12 months Foa examined the testicles of the pinealectomized birds and found that they were not only increased in size, but also showed that the general increase was due to the hypertrophy of both the interstitial tissue and the seminiferous tubules. He obtained similar results by repeating these experiments on rats and mice and another series of young chicks. In the latter series he noted that the size was not so markedly influenced as in the first series, and also that pinealectomy had no effect on hens.


PINEALECTOMY 423

Izawa performed pinealectomy on 36 chickens ranging from 4 to 5 weeks of age, and besides these 1 1 others of the same age and weight as those operated on were used for comparison. Aseptic precautions were taken, and no cases of infection occurred. Most of the experimental animals died shortly after the operation. Only four — three males and one female — survived the operation for any length of time. These were fed under the same conditions as the control animals and the effects observed. Compared with the controls, the pinealectomized animals showed a retarded growth for a few weeks following the operation, but about a month later they grew more rapidly than the controls, their body-weight becoming greater and their legs longer than those of the controls. In the two males whose pineal bodies were completely removed, the rapid development of the comb and the premature crow deserve special notice, and Izawa stated that they gave evidence of sexual instinct 31 and 50 days earlier than the controls. There was also a marked increase in the size of the testes.

In the female pinealectomized bird there was a remarkable increase in the size of the ovary and of the Fallopian tube, the latter showing a great increase in the length of the tube with increase in the width of its ampullary portion, which was described as voluminous, while the Fallopian tubes in the control were not only short but uniformly slender throughout their whole length.

Zoia and Horrax also report positive results following pinealectomy. The latter states that pinealectomized hens tend to breed earlier than controls of the same age and weight ; on the other hand, Sarteschi reports that pinealectomized hens dislike to copulate. Izawa gives tables showing the exact weight and size of the various organs and parts of the animals experimented on, and of the controls. From the statistical side it should be borne in mind that the results obtained by Izawa, striking as they appear to be, were based on only three cases, two male and one female, and that the controls were individuals matched with regard to age and weight with the experimental animal rather than of average size and weight.

Positive results following pinealectomy have also been recorded by Urechia and Gregoriu, Hoffmann, Zoia, Clemente, Izawa, and Yokoh in young rats and chickens, namely, general increase in the growth of the body and increase in the size and weight of the genital glands in both males and females. Hoffmann also found in three pinealectomized rats a decided enlargement of the vesicular seminales.

Horrax, 19 16, experimenting with rats and guinea-pigs, found acceleration of spermatogenesis in the pinealectomized animals.


424 THE PINEAL ORGAN

Pinealectomy Resulting in Negative or Regressive Effects

Kolmer and Loewy destroyed the pineal gland by cauterization in immature rats weighing 50 grm. They obtained negative results and verified histologically that the destruction of the organ was complete.

Cristea practised epiphysectomy in 30 male chicks, 12 of which survived, and in place of increased growth showed a rapid retardation of both general development and of secondary sexual characters.

Foa's experiments, previously mentioned, were negative with respect to chicks of the female sex.

Dandy, who experimented on dogs, came to the following conclusions :

1. Following the removal of the pineal he observed no sexual pre cocity, or indolence ; no adiposity or emaciation ; no somatic or mental precocity or retardation.

2. The experiments seemed to yield nothing to sustain the view

that the pineal has any active endocrine functions of importance either in very young or adult dogs.

3. The pineal is not essential to life and seems to have no influence

on the animals' well-being.

Demel performed epiphysectomy on rams aged 4 weeks, of which four survived. These showed a diminished growth, they became timid, their fleece was poor and diminished in amount, their horns grew very slowly and in two of them the horns were shed. The testicles were as large as those of the healthy rams or definitely larger (positive change). The hoofs were defective and there was an increase in the body temperature, which was raised by more than 1 ° C.

As a counter-test, Demel fed these animals for three months with " epiglandol." They rapidly recovered, attained the weight of the control rams, and developed the normal amount of fat and their horns. Demel came to the conclusion that the pineal played a role in the regulation of temperature and in producing hypertrophy of the testicles. He considered that it had no effect on the secondary sexual characters. But, since as is well known, the development of these is associated with the development of the genital organs, it is difficult to believe that the one system could be affected without the other. It is possible also that the rise of temperature and poor condition of the experimental animals might have been due to concomitant injury of the meninges and other important parts, and the subsequent improvement in their condition to recovery from this, quite apart from the action of epiglandol.

Negative results were also obtained in lower vertebrates, e.g. frog tadpoles, by Atwell and E. R. Hoskins and M. Hoskins. In those animals


PINEALECTOMY WITH NEGATIVE EFFECTS 425

which survived complete destruction of the pineal body by means of a thermocautery, nothing abnormal was observed in their development.

In one of the most recent publications on the effects of pinealectomy, namely, by L. G. Rowntree in the Practitioners' Library of Medicine and Surgery, 1938, Chapter 5, this author summarizes the general results of this operation in the following words : " Pinealectomy in the hands of many investigators has led consistently to negative results ; in the rat (Foa, Horrax, Kolmer, Loewy, del Castillo, Renton and Rushbridge, Anderson and Wolf) ; in the rabbit (Exner and Boese) ; in the dog (Dandy) ; and in the chick (Badertscher). Positive results have been claimed in the rat by Izawa and Yohoh ; in the guinea-pig (Horrax and Clemente) ; and in the chick (Foa, Zoia, and Clemente). The most common results of pinealectomy are said to be : premature development of secondary sexual characters in the male ; enlargement of the gonads, overgrowth of the body, and obesity. Anderson and Wolf, after a critical analysis of the several papers submitted, expressed the opinion that the data submitted do not justify the conclusions reached."


The Effects of Feeding with Pineal Substance and the Injection of

Pineal Extracts

Precocious sexual and mental development and early somatic development when occurring in the human subject are usually interpreted as indicating pineal deficiency or hypopinealism. If this opinion is correct, one would expect that feeding with pineal substance or the injection of pineal extracts would produce a condition of retarded sexual and mental development and deferred somatic maturity. The effect of feeding experiments, however, appears in many instances to be just the reverse, namely, in place of inhibition of growth of the sexual organs and of the body, there is often a rapid sexual and somatic development. There are, however, a considerable number of experiments which have given results which appear to confirm the general opinion of the restraining influence of the pineal and which may, according to Calvet, be regarded as positive in nature, whereas the accelerating and stimulating influence may be regarded as negative.

Positive Effects. — Sisson and Finney obtained a retardation of growth in young rats by feeding with the epiphysis of the calf. Priore found that repeated injections of pineal extracts produced a definite retardation of development in young male rabbits. M'Cord and Allen dissolved the desiccated powder of the pineal in water containing living Amblystomes [

1 The type of this group of tailed amphibians is the Mexican axolotl, which is the permanent larval form of a salamander from the United States, Amblystoma tigrimon.


426 THE PINEAL ORGAN

and obtained a retardation of metamorphosis. This result is, however, counterbalanced by the results of experiments published by M'Cord in 1 91 7, in which he states that : "In unicellular organisms (paramoecia) pineal extract increases the rate of reproduction to more than double that of the controls " ; and " in larval forms (Ranidce) both growth and differentiation are hastened."

Berblinger, experimenting on young rats, injected alcoholic and watery extracts of the epiphyses of oxen subcutaneously, and also administered the pineal by way of the alimentary tract. He obtained positive results in most, but in some there was an increase in size.

Calvet also experimented on immature white rats, using epiphyseal extracts obtained, fresh, from entire horses, geldings, and mares. These were ground aseptically in a mortar and mixed with equal parts of physiological serum. The animals received daily injections of this solution for 8 days, and were killed two days after the injections had been discontinued. The testicles were slightly smaller than those of the controls, but the size of the animals remained practically the same as the controls.

Negative Results. — M'Cord fed young chickens and guinea-pigs with food containing a mixture of desiccated pineal gland and lactose. The control animals received a similar food containing the same amount of lactose but without the pineal. In both cases there was an acceleration of growth in the experimental animals. At the end of two weeks the guinea-pigs fed with pineal substance showed an increase in weight of 100 per cent., as compared with an increase of 77 per cent, in the controls. The author, however, noted that the action was variable (Fig. 283), and that if young animals were fed with epiphyses obtained from aged oxen, there was a diminution in weight.

Negative results, namely, acceleration of development and increase of weight, have also been obtained by Roux in frog tadpoles, Calvet in tadpoles of Alytes, M'Cord (previously mentioned) in Ranidce, by feeding with desiccated epiphysis, and also by Calvet with daily injections of Epiglandol into immature rats, 1 c.c. of Epiglandol being equal to 0-02 grm. of the fresh gland. The injected animals killed three weeks after weighed 34 grm., while the largest of the controls weighed only 31 grm. Notwithstanding this somatic increase, the testicles were not hypertrophied and macroscopically appeared even smaller than those of the controls ; moreover, microscopical sections showed no appreciable change in structure.

In discussing the various results of these experiments depending on the use of desiccated epiphysis or extracts of the epiphysis, Calvet puts forward the suggestion, based on the biochemical researches of Fenger and Roux, that since phosphoric acid, calcium, magnesium, sodium, and


EFFECTS OF FEEDING WITH PINEAL EXTRACTS 427

other inorganic elements are present in the desiccated epiphysis it is possible that the power to influence growth may be due to the action of these chemical constituents rather than on the supposed action of a hormone.

Robinson reports further feeding experiments carried out by M'Cord on young animals using fresh pineal glands, with resulting early precocity and adiposity ; Hoskins' results were almost completely negative. Kozelka also obtained negative results with pineal implants in chicks ; whereas increased rate of growth has been claimed by Dobowik ; and in the rat




i <


Fig. 283. — A — Control Bird, and B — Experimental Chick nourished with a Desiccated Extract of the Epiphysis, obtained from young Oxen.

The experimental chick is diminished in size ; feeding with the extract has, therefore, in this instance retarded growth.

(Redrawn from Calvet, after M'Cord.)


Lahr found no influence on body-growth in either sex, but retardation of gonadal development in both male and female animals. Robinson further records the experimental work of Hanson on the effects on the offspring of intraperitoneal injections of pineal extracts in successive generations of parent rats. In succeeding generations up to the fifth he obtained increasing retardation of growth, with acceleration in gonadal development, precocity, " dwarfism," and macrogenitalismus precox being the outstanding results.

Incidentally it may be mentioned here that observations on the human subject seem to indicate that in those cases in which excessive premature growth of the body has been associated with mental and sexual precocity, the ultimate stature and body-weight of those individuals who have lived to adult life is below the average height and weight.

In an interesting article by H. Lisser in Bedside Diagnosis, 1928,


428 THE PINEAL ORGAN

W. B. Saunders, Philadelphia, the author, refers to certain cases of hypergenitalism in preadolescent males combined with premature union of the epiphyses of the long bones. The principal signs being : premature and excessive development of the genital organs ; premature change of voice, associated with rapid and excessive development of the body in general ; the mental development, although somewhat precocious, not keeping pace with the general precocity, and in addition to the above-mentioned well-recognized group of symptoms, under the heading of skeletal changes, Lisser states that " the boy is large for his age, as if he were becoming a giant, but the excessive output of testicular secretions hastens epiphyseal unification, and the premature union of the epiphyses transposes a misleading and transitory gigantism into a final height which is not excessive and which may indeed incline to a mild form of dwarfism. Roentgenograms on such boys will reveal a bone age in advance of their chronological age as an additional proof of precocity."

It seems possible that this explanation of premature bodily growth associated with excessive testicular secretion and premature union of the epiphyses may account for some of the apparently contradictory results of experimental work on the effects of feeding with pineal substance or extracts, or injections of pineal extracts, namely: in some retardation or arrest of growth, " dwarfism," while in others there has been excessive growth. It must be borne in mind, however, that in a large proportion of the clinical cases that have been recorded in which these symptoms have been present there is no proof of their having been connected either directly or indirectly with the pineal organ.

The Influence of Pineal Grafts

Calvet experimented on three rats belonging to the same litter. These animals received every second day one-half epiphysis of an entire adult horse, which was introduced into the subcutaneous tissue of the dorsal region with aseptic precautions. The control animal received a portion of muscle or cerebral substance of equal weight from the horse and suffered the same traumatism as the experimental animals. The grafts commenced on the 15th November, 1932, and ceased on the 10th December. The weight of the control rat, which at the commencement of the experiment was 38 grm., reached 62 grm. The others treated with the epiphysis weighed 40 grm. at the commencement, decreased 3 grm. from their original weight. The normal rat increased 3 cm. in length, while the size of the grafted animals remained stationary.

Moreover, the migration of the testicles was arrested in the grafted animal, and microscopic sections of the testicle showed a true atrophy,


INFLUENCE OF PINEAL GRAFTS 429

whereas the testicles of the normal rat had migrated into the scrotum and showed active spermatogenesis. Calvet repeated the same experiment on a number of rats and young guinea-pigs and obtained practically the same results.

Grafts carried out on adult males were without effect on either growth or the testicles.

Hblldobler and Schultze obtained acceleration of metamorphosis with increase of weight after implantation of a small piece of the epiphysis of the ox at the root of the tail in the larva of the toad, their results are opposed to those of Calvet and are classed by him as negative. On the other hand, the same experiment was repeated by Romeis, who was unable to confirm the result of the last-mentioned observers.

Correlation of the Pineal Gland with the Genital Glands and other Endocrine Organs

An interesting observation which appears to indicate an interrelationship of the pineal organ and the genital glands was made by Jean Calvet, namely, that the parenchyma cells in the pineal gland of the bullock are less numerous than in that of the bull, and also that the neuroglial tissue is relatively more abundant in the castrated than in the entire animal. This observation is of considerable importance and if confirmed by subsequent investigations on similar lines with a detailed record of the age of the animals from which the epiphyses were obtained would be of real value in establishing the existence of a definite interrelationship between the pineal gland and testicles.

Biach and Hulles (19 12) found in cats which had been castrated when very young that 7-8 months after there was an atrophy of the parenchyma of the pineal, and he also stated that the epiphysis of the ox was smaller than that of the bull. Calvet also weighed the epiphyses of geldings and oxen and compared these with the weights of the pineal body in stallions and bulls. The results were variable, the glands being sometimes larger in the castrated than in the entire animals, but the weight of the pineal glands of the stallions and bulls was on the whole greater than in the castrated animals and they were more developed.

Aschner (191 8),' moreover, has confirmed the observations of Calvet with regard to the predominance of neuroglial fibres and fewer nuclei of the parenchyma cells of the pineal gland in the ox as compared with the bull, and has noted the same differences in dogs, cats, rabbits, and guineapigs.

1 Aschner, B., Die Blutdriisenerkrangimgen des Weibes. (Wiesbaden, 191 8.) Physiologic der Hypophyse. Handbuch der inneren Sekretion, II, Liefkabitzsch.