Experimental studies on the effect of cortisone on histological changes of the endocrine glands induced by toxic doses of fat soluble vitamins
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
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
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
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.