지용성비타민 중독량투여로 인한 내분비선의 변화와 이에 미치는 Cortisone의 영향

Abstract

[한글]

[영문]

The toxic effects vitamin A caused by ingestion of large quantities of polar bear

liver has been reported by Kane in 1857 and by numerous investigators in that field

thereafter. The studies on histopathologic changes due to hypervitaminosis A on

various organs such as the skeleton, kidney, skin and liver were reported by many

workers while Ko(1959) found that hypervitaminosis A brought about degenerative

changes of endocrine glands such as pituitary gland, thyroid gland, pancreas,

adrenal gland and testicles. In animal experiments, Selye(1958) ascertained that

cortisone accelerates skeletal changes produced by vitamin A toxicosis. On the

contrary, Fell(1962) indicated that cortisone does not accelerate any pathological

changes in the cartilage.

On the other hand, Hess(1928) reported vitamin D intoxication in infants treated

by ultraviolet irradiated ergosterol and since then many workers have reported

hypervitaminosis D or vitamin D sclerosis. In the treatment of vitamin D

intoxication, the administration of cortisone produces a marked reduction in the

blood concentration of calcium, and an alleviation of various toxic aigns.

Dent(1953) observed a reduction in the absorption rate of calcium in the

gastrointestinal tract and also a lowered blood calcium concentration by cortisone

treatment in the patients of sarcoidosis which was associated with hypercalcemia.

Moreover, Thomas and Morgan(1958) noticed an improvement of toxic signs of

hypervitaminosis D by the administration of cortisone in animal experiments. Clark

and Bassett(1960) described that the weight loss and the calcium deposit in the

soft tissue, which were caused by hypervitaminosis D, can be prevented by the

administration of large quantities of vitamin A.

In view of theses considerations the author attempted to study effects of

cortisone on the changes of endocrine glands in hypervitaminosis A, and effects of

cortisone on the changes of endocrine glands, induced by a combined administration

of toxic dosed of vitamins A and D, in normal rats.

36 rats were subdivided into the following 6 groups, each consisting of 6

animals.

Group 1. This group is the control group, consisting of rats fed on stock diet

and 500 I.U. of vitamin A/gm of body weight/day by stomach tubing for 3 weeks.

Group 2. This group is also the control group, consisting of rats fed on stock

diet and 60 I.U. of vitamin d/gm of body weight/day by stomach tubing for 3 weeks.

Group 3. This group consisted of rats which were fed on a stock diet and, in

addition, received orally 60 I.U. of vitamin D/gm of body weight/day and also 500

I.U. of vitamin A/gm of body weight/day for 3 weeks.

Group 4. This group consisted of rats which were fed on stock diet and, in

addition, given 0.05mg of cortisone acetate/gm of body weight/day(I.M.) for 3

weeks.

Group 5. This group was placed on the same regimen as Group 1. In addition,

0.05mg of cortisone acetate/gm of body weight/day was intramuscularly administered

for 3 weeks.

Group 6. This group was placed for 3 weeks on the same regimen as Group 3 and, in

addition, 0.05mg cortisone acetate/gm of body weight/day for 3 weeks.

At the end of 3 week experimental period, the rats were sacrificed by injecting

air into the heart. According to these experiments, the changes on the anterior

pituitary gland induced by administration of toxic doses of vitamin A were

relatively mild; the nuclear pyknosis of acidophilic cells including slight changes

in basophilic cells were observed while cortisone affected more remarkable to the

above changes.

The degenerative changes of the thyroid gland due to the administration of toxic

doses of vitamin A were aggravated by cortisone adminstration, and the outstanding

change to be noted were desquamation of acinar cells and nuclear pyknosis. Main

pancreatic changes induced by toxic doses of vitamin A were atrophy of ductal

cells. Cortisone administration resulted in hypertrophy of Langerhan's islet and a

considerably severe atrophy of ductal cells in general. Changes of the adrenal

gland produced by toxic doses of vitamin A were a slight hypertrophy in zona

faciculata and hyperemia in the medulla. These changes became more remarkable

administration of cortisone.

Changes in the testis with the toxic doses of vitamin A were atrophy of

seminiferous duct, proliferation of Sertoli's cell followed by degenerative changes

and slight proliferative changes in stroma. These changes also became more marked

by the cortisone administration. Changes on the anterior pituitary gland caused by

a combined administration of toxic doses of vitamins A and D were very mild as

compared to those seen when vitamin A alone was given. When cortisone was

additionally given, moderate to severe changes in basophilic cells and a clear-cut

vaculization of the cell were found. Effects on the thyroid gland were again milder

in case of a combined vitamin A and D administration than in administration of

vitamin A alone.

In the pancreas, only a slight condensation of ductal cells and zymogen

granulations have been observed in the groups of toxic doses of vitamin A and D. In

contrast, a high incidence of acinar cell desquamation was observed when vitamin A

alone was given. Pancreatic changes induced by a combined administration of

vitamins A and D were a mild degree of condensation of ductal cells and a reduction

in zymogen granulation; these changes were considerably milder than those seen when

vitamin A alone was given. Changes induced by cortisone were pyknosis of ductal

cells and a slight hypertrophy of Langerhan's islet. Toxic doses of vitamin A and D

induced a very mild change on the adrenal gland. Severe degenerative changes in

zona glomeruloza and zona faciculata have been observed by cortisone

administration. Testicle changes induced by toxic doses of vitamins A and D were

degeneration of the seminiferous duct, proliferation and hyperemia of interstitial

cells. These changes were more prominent when cortisone is administered; a

reduction in sperm formation, degeneration of the seminiferous duct and

proliferation of the sertoli's interstitial cell were observed.

These results indicate that cortisone aggravates while vitamin D alleviates

morphological changes of various endocrine glands, induced by a toxic dose of

vitamin A, although both cortisone and vitamin D themselves induce morphological

changes of endocrine glands. However, the underlying mechanism(s) for these

interesting effects are not clear at present.