대량의 황산동 투여가 백서의 부신 및 뇌하수체에 미치는 영향에 관한 형태학적 연구

Abstract

[영문]

[한글]

Merphological Effect of Excess Copper Sulfate on the Adrenal Gland and Anterior

Hypophysis of the Rat

Sang Ho Cho, M.D.

Department of Medical Science, The Graduate School, Yonsei University

(Directed by Prof. Dong Sik Kim, M.D. and Prof. Yoo Bock Lee, M.D.)

The mechanism by which copper exerts its toxic effect on the hepatic cells in

Wilson's disease is not known yet.

Attempts to produce hepatic dysfunction and morphological lesions equivalent to

Wilson's disease in experimental animals have been unsuccessful. Experimentally

induced deposits of copper in hepatic cell generally do not produce necrosis or

cirrhosis (Howell, 1959 ; McNary, 1963; Barka et al., 1964).

Recently, results of many experiments on this subject suggested that

sequestration of copper by lysosomes may protect hepatocytes from toxic effects of

this metal (Goldfischer and Moskal, 1966; Goldfischer, 1967; Goldfischer and

Sternlieb, 1968; Goldfischer et al., 1970). The corticosteroid is known to

stabilize lysosome in vivo (Weissmann, 1965).

According to the results of many experiments, one of the consequences of

adrenalectomy or hypophysectomy in rats is an increased ceruloplasmin with a

restoration of normal levels when the animals are given corticosterone (Evans and

Wiederanders, 1968; Gregoriades and Sources, 1969: Evans et al., 1970). On the

basis of these results, Evans and Cornatzer (1971) have considered that following

adrenalectomy or hypophysectomy, bile flow was significantly decreased suggesting

that adrenal steroids regulate biliary copper excretion by choleretic action.

But studies of the role of the adrenals in the metabolism of copper have been

concerned mainly with effect of adrenalectomy and of certain corticosteroids on the

activity of plasma ceruloplasmin (El-Mofty et al., 1959; Evans and Wiederanders,

1967, 1968).

Attempting to gain a better understanding of the role of the adrenals in copper

metabolism, the influence of administration of excess copper on both adrenals and

anterior hypophysis is examined.

Materials and Methods

Adult female albino rats were divided into two groups and treated as follows:

Group Ⅰ: Normal control 24 rats

Group Ⅱ: CuSO^^4 treated 84 rats

In experimental group, 0.3 c.c. of 0.5% copper sulfate solution was given

intraperitoneally per animal daily and 0.3 c.c. of distilled water was given by

same method in control group. At 1st, 3rd, 5th, 7th, l0th, 15th, and 30th days, 12

rats were killed in experimental group and 6 rats in control group by

exanguination.

The unfixed adrenals and pituitary glands were weighed on the chemical balance in

order to verify enlargement.

For light microscopic examination, adrenals and liver were fixed in 10% neutral

formalin and pituitary glands were fixed in Zenker's solution. They were embedded

in paraffin and stained with hematoxyli-eosin. Additionally, liver sections stained

with diethyldithiocarbamate stain (Howell, 1959) and pituitary sections stained

with P.A.S. reaction. Sudan stain with the adrenal sections were performed.

Specimens for Schultz reaction were obtained from the adrenal gland. The

specimens were fixed in formol-calcium for 2 to 3 days and cut 10μ frozen

sections. And then they were washed for 24 hours in several changes of distilled

water, placed he sections into ferric ammonium sulfate solution for one week at

37℃ washed sections in 3 changes of acetate buffer one hour in each, rinsed

quickly in distilled water, placed in 5% formalin for 10 minutes, mounted on

slides, applied a drop of acetic-sulfuric acid mixture (1:1) to a cover slip and

examine immediately under the microscope.

Results and Summary

1) The intracellular deposition of copper was increased gradually, but neither

hepatic cell necrosis nor cirrhosis were noted throughout the whole experimental

period.

2) The excess amount of copper sulfate loading caused increased weight and

hyperplastic changes of zona fasciculata and zona reticularis combined with

increased accmulation of lipids in adrenal gland of adult rat after the

administration as early as the first day. And also increased functional activity

was induced. However, these hyperplastic changes and increased functional activity

in adrenal gland did not progressively increase as copper loading increased.

3) In anterior hypophysis, increased weight and hyperplastic changes of beta

cells were caused after the administration of the first day. But these changes did

not progressively increase as copper loading increased.

On the basis of the above results it is speculated that an increased amount of

adrenocortical hormones as a result of adrenocortical hyperfunction, mediated by

the pituitary, in excess copper loaded rats may protect the hepatic cells from the

toxic effects of excess copper.