INFLUENCES OF EXCESSIVE EXERCISE ON THE STRUCTURE AND FUNCTION OF RAT ORGANS KAZUO ASAHINA, FUJIKO KITAHARA, MIYOKO YAMANAKA AND TOSHIKO AKIBA* Department of Physiology, School of Medicine, Toho University, Tokyo In this experiment, the effect of excessive exercise on the sexual cycle and histological changes of various organs of albino rats were observed. Of the sexual cycle of albino rats Gotoda (1) found that the fatigue caused by vibration brings about a considerable prolongation of the anestrus period. Hirai (2) made a comparative histological study on the myocard and skeletal muscle of animals which habitually move actively and those which do not move so much. Ogawa (3) made albino rats swin and measured changes in the weight of the principal organs. Selye (4, 5) investigated histological changes in each stage of stress reaction and reported that the hypersecretion of the adrenal cortical hormone and pituitary ACTH, hemorrhagic ulcer in stomach and intestine, nodular myocarditis, perivasculitis, abnormal swelling of renal tubuli and the degenerative change of thymus could be seen. METHOD Experiments were made on albino rats weighing 120-150g. using a method requiring forced swimming in a tank. Tests were made in the following three groups:a group (excessively trained):trained for 60 or over 90 days. B group (castrated and excessively trained):4 weeks after castration, 60 days training was applied. C group (untrained):untrained rats were forced-swum. For the test of the sexual cycle, 36 rats were selected whose sexual cycle (vaginal smear method) were comparatively regular. At first they were given light exercise of 10-30 minutes swimming and gradually the time was extended and by 17 days the training lasted 3-6 hours daily. The vaginal smear was examined before the exercise and if deemed necessary several times a day at an interval of two hours. The sexual cycle was divided into 4 phases according to Zondek and Aschheim; prestrus (P), estrus (E), metestrus (M) and diestrus (D). Histological changes in various organs were observed under ordinary staining, but according to necessity the fat, hemosiderin and calcium were examined under special staining. Received for publication October 29, 1958. 322
EXCESSIVE EXERCISE 323 RESULT The sexual cycle appeared regularly when the light or moderate exercise were applied, but with the heavy training, it showed an extension in (P) and (E) and later a long lasting anestrus. In such cases the sign of (E) could not be noticed even by repeated examinations. The irregular appearance of (E) was usually associated with the fall in body-weight. There were some animals which showed an extention in (E) before the training were applied, but they showed a comparatively perfect cycle when they were moderately trained. There were some cases, however, in which the moderate training of 1-2 hours swimming resulted in an extension of (P) and (M), and some other cases in which the heavy training of 3-6 hours caused the extension of anestrus but (E) could be seen in an interval of 7-10 days. One of these cases is shown in fig. 1. FIG. 1. Effect of heavy exercise on the estrus cycle 2. Histologicals a ) Thyroid gland:within 20-30 days of training the follicles developed and the follicular cells became high in shape. The gland showed a picture of a general hyperfunction associated with a moderate hyperemia, but later the degenerative change occurred. In the 90 days training group, the destruction of the follicular epithel and of the follicles, and the atrophy or hyperplasia of interstitial tissues were evident. b ) Adrenal gland:in the first stage, the hypertrophy of the adrenal cortex, cell infiltration, the increase in the pigmental granules, fat deposition and hyperemia were recognized and later, the general degenerative changes and atrophy were seen. c ) Hypophysis:Hypophysis showed a picture of hyperfunction with moderate hyperemia in the early stage of training, causing degranulation of the acidophilic cells and enlargement of the basophilic cells. d ) Pancreas:In the 20-30 days group the parenchymal cells of the Langerhans isletes increased in number showing a picture of hypersecretion. e ) Thymus Even in the 30 days group the decrease of cortical lymphocytes with the production of juvenile cells, atrophy and the diminution of Hassal's corpuscles were recognized. In the 60 days group these changes became conspicuous and in the 90 days group the parenchym was markedly atrophied and replaced by adipose tissue.
K. ASAHINA 324 f ) Salivary gland:no marked change ET AL. was seen even in 60-90 days group. g ) Circulatory organ:myocardiac fibers were seen hypertrophied in the 30 days group, but it was notable that the fibers in the right ventricle tended to atrophy. In the later stage, the interstitial cell infiltration which reminds one of the softening lesion or myocarditis appeared and moreover, the cartilage was seen in the aortic valve in some cases. h ) Respiratory organ:in the 20-30 days group, hyperemia, emphysema and partial atelectasis appeared with the hyalinization and edematization in perivascular tissues. With the extention of training the atelectasis became prevailing and the perivascular and peribroncnial cell infiltration became evident. i ) Digestive organ:stomach and intestinal mucous, villi and muscle layer hypertrophied with the edematous appearance. Thus the acceleration of mucous secretion with hyperemia were recognized. But later the mucous layer atrophied and became extremely thin and the secretion was definitely restrained. (fig. 2). Acidophilic cells increased in number and this can be seen most apparently in heavily trained group. FIG. is ced very 2. thin; Intestine mucosa in and the villi heavily extremely trained rat. atrophied Muscle with layer redu- secretion. The liver gradually decreased in weight after an increase in the first 20 days. Marked hyperemia, stagnancy and edematization in liver were seen in the 20-30 days group, but later the liver atrophied resulting in cell infiltration and hyperplasia of interlobular connective tissue. Furthermore the dark pigment in the stellate cells, which was not hemosiderin, appeared. j ) Urinary organ: As in other organs, the weight of kidney showed an increase at the early stage followed by gradual decrease. From the histological point of view the kidney showed the extremc changes as compared with the other organs. In the 20-30 days group, the hypertrophy of the glomerulus, hyperemia and swelling of tubular epithel were seen and
EXCESSIVE EXERCISE 325 the calcium deposition in tubulus was found in the 70 days group. Furthermore, in 90 days group, the glomerulus showed progressive atrophy, hypermemia or anemia, and a considerably strong destruction. And the tubular epithel showed a strong cloudy swelling which was seen in the renal pelvis as well (fig. 3). FIG. 3. Kidney in the heavily trained rat. high grade destruction of glomerulus. Edematous tubules; DISCUSSION The training provided a good influence on the irregular sexual cycle so far as it was not too hard. But in all cases where the heavy exercise was applied, the sexual cycle was severely disturbed. It has long been clinically ascertained in man that the hard labor results in impregnancy and irregular menstruation or amenorrhoe as Iwata (6) and others reported. Selye attributed this to the hypophyseal conditions and stated as follows:due to the fact that as corticotropic hormone is unavoidably overproduced, the production of other pituitary hormones, especially that of gonadotropic hormone is sacrificed, resulting in the degranulation of the acidophilic cells and enlargement of basophilic cells which shows the picture of hypophyseal hyperfunction. Richter (8) showed a rat that became obese subsequent to 8 days of forced swimming and attributed this to the tumor found in the pituitary gland. In this experiment, however, even in cases with long lasting anestrus, the atrophy of ovarium was comparatively slight and the follicles were seen in the developing stage. This may be due to the shift of production of the pituitary hormones. But the histological finding in the ovarium does not necessarily coincident with the picture of the vaginal smear. However, in cases of extremely heavy exercise, an extreme atrophy may occur in ovarium and the degeneration of the ovarial follicles became strong and a large number of atrophied corpus luteum was recognized. It is evident that the adrenal cortex has a close relation to the bodily exercise. Ingle (7) reported that several months of training would cause hyperemia and hypertrophy in the adrenal cortex and the extract of adrenal cortex had a favorable effect to fatigue. Selye also stated that the adrenal
326 K. ASAHINA ET AL. cortex showed hypertrophy when stress was given. Also in this experiment the adrenal cortex reacted to the exercise promptly. Thymus is an organ which degenerates most easily. In this experiment the degenerative changes were recognized even in the minor exercise group, and further, in the exhaustive period, a more marked picture of atrophy was seen. Even in the exhaustive period of the heavy trained group, however, not many changes were seen in salivary gland and testicle gland, thus these glands seem to be structures of the largest resistance. Digestive tract showed the picture of hypersecretion in early stage and the marked atrophy in the later stage in this experiment. Kidney showed more severe changes than in other organs in this experiment. But the urine protein or other abnormal substances did not appear so much that could be expected from its histological changes. Now, in the castrated group, there was a tendency that the atrophy or degeneration appeared in all organs earlier than in the uncastrated group. Thus the sexual hormone might have some important role in training. SUMMARY Some discussions were made on the alteration of estrus cycle and histological changes in various organs caused by excessive training to albino rats. In the lightly or moderately trained group, the sexual cycle rotates regularly and even if it had been irregular prior to exercise, it became regular with training. In heavily trained group, there occurred an irregularity in the sexual cycle associated with the conspicuous decrease in body-weight. In general, most organs showed the figure of hyperfunction in the early stage of training and degeneration or atrophy in later stage. Among others, thymus is the most fragile tissue, and salivary gland and testicle gland are the most resistant tissues against excessive exercise. The histological changes in intestine and kidney were very severe for their comparatively slight functional disturbances. REFERENCES 1. H. GOTODA. Ni-san-Kaishi 2:411, 1950. 2. T. HIRAI. Kaibogaku-Zasshi 21:545, 1943. 3. S. OGAWA, Sugimoto-Kenkyu-Ronbun-Shu 2:195, 347, 1951. 4. H. SELYE. J. Clin. Endocrinol 6:117, 1946. 5. H. SELYE. The story of the adaptation syndrome. Montriol:Acta. Inc. Medical publishers, 1952. 6. S. IWATA. Sanfujinka-no-Sekai 7:478, 1955. 7. D.J. INGLE. Am. Int. Med. 35:652, 1951. 8. C.P. RICHTER. Neurological basis of behaviour, P. 204. J. and A. Churchill Ltd. 1958.