A COMPARATIVE STUDY OF THE OVARIES AND OTHER
ENDOCRINE GLANDS IN RATS WITH BENIGN TRANSPLANTED BREAST TUMORS AND I N NORMAL RATS
INJECTED WITH SEX HORMONES
JACOB HELMAN, M.D.
(Prom the Institute of Cancw Research, Columbia University, Francis Carter Wood, Director)
Some two years ago a paper appeared recording the writer's studies on the
influence of hormones on breast tumors and breast hyperplasia in rats. A
study of the ovaries in the same groups of animals was undertaken to ascertain
whether structural changes occurred which were in any way related to the
transplanted mammary tumors or to the hyperplasia of the breasts induced
by subcutaneous injections of antuitrin S and theelin.
One hundred and fifty-five rats of the Laboratory Sherman breed, between
the ages of six and eighteen imnths, were examined. They were divided into
the following groups:
Rata with subcutaneoue transplanted mammary tumors . . . . . . . . . . . .
Rats immune to tumor growth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Control rats ...................... . . . . . . . . . . . . . . . . . . . . . . . . . . .
Normal rats injected with sex hormones ..........................
57
10
10
78
Among the 5 7 tumor-bearing rats, breast tumors occurred in the following
percentages:
Fibro-adenomata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Adenomata and cystadenomata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Fibromata and fibrosarcomata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
46.6%
9.0%
44.4%
The ovaries were graded according to the number of graafian follicles,
corpora lutea, involuted or atretic bodies, and visible cysts. In the tumorbearing rats few or no follicles were visible in the ovaries. The large corpora
lutea present in this entire group differed in no way from those in control 'adult
females twelve to eighteen months of age. Young tumor-bearing rats showed
few follicles and many large corpora lutea in the ovaries.
Ovarian cysts were present in 29.8 per cent of all tumor-bearing rats.
They occurred in 83 per cent of the rats with transplanted cystadenomata or
adenomata of the breast, in 26.9 per cent of those with fibro-adenomata, and
in 10 per cent of those with fibromata. None was discovered in rats with
transplanted sarcoma. Of the immune and control rats, 10 per cent had
ovarian cysts. It is noteworthy that in 90 per cent of the animals immune
to the growth of the transplanted fibro-adenoma, the ovaries were small and
shrunken, showing many atretic bodies. Of the 78 normal rats injected with
estrogenic and gonadotropic hormones, 47.9 per cent showed ovarian cysts,
and 37 per cent marked breast hyperplasia.
The above observations corroborate many of the known facts concerning
the hormonal relationship of breast and ovary. Of particular interest is the
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587
OVARIES AND OTHER ENDOCRINE GLANDS IN RATS
observation that rats with transplanted benign epithelial breast tumors showed
a higher incidence of cystic ovaries than those with connective-tissue tumors.
Some of the rats with transplanted fibro-adenomata or adenomata had,
in addition to cystic ovaries, cysts in the adrenal, thyroid, and pituitary glands.
Similar cystic changes appeared in the adrenals and thyroids of normal rats
which were injected with combined estrogenic and gonadotropic hormones.
These injected rats showed very marked breast hyperplasia and early stages
of benign tumor growth. Not a sufficient number of animals with multiple
cysts of the endocrine system were available, however, for conclusive statistical
observations. In the group of animals studied, exclusive of the 10 controls,
cysts were found in the thyroid or pituitary gland or breasts in 15.5 per cent.
Ovarian cysts occurred in 32.1 per cent, more than double the percentage for
all the other endocrine glands combined.
The following tabulation shows that the proportion of ovarian cysts in
injected animals and tumor-bearing animals is similar to that of cysts of the
remainder of the endocrine system in the two groups.
In 145 adult white female rats (uninjected controls not included) there occurred :
Cysts of ovaries . . . . . . . . . . .
32.1%
Cysts of other endocrine glands
15.5%
Ovarian cysts occurred in
Tumor-bearing animals . . . . .
Injected animals (no tumors)
Tumor-bearing injected animals .
Cysts of other endocrine glands occurred in
Tumor-bearing animals .
Injected animals (no tumors)
Tumor-bearing injected animals
29.0%
35.3%
47.9%
7.1%
10.9%
19.7%
From these figures it is obvious that among tumor-bearing animals which
received hormone injections the incidence of cysts in the ovary and in the
other endocrine glands was bigher than among non-injected animals. A few
of the injected animals showed cystic kidneys, probably due to the elimination
of large amounts of estrogenic substance in oil. Old castrated rats, whether
tumor-bearing or injected, had a high percentage of thyroid cysts. Immune
rats injected with antuitrin S alone showed follicular cysts, while antuitrin G
was without effect on the ovaries. One old male rat with a large spontaneous
fibroma had cystic degeneration of the testes.
DISCUSSION
It is difficult to state whether or not the presence of ovarian cysts in this
group of tumor-bearing animals is a mere coincidence. Rats with transplanted
mammary cystadenomata or adenomata showed the highest percentage of
ovarian cysts, while in animals resistant to these benign transplanted tumors
involution of the ovaries was observed. This suggests more than a casual
relationship. Furthermore, a comparison between non-tumor-bearing animals injected with antuitrin S and theelin and uninjected tumor-bearing ani-
588
JACOB HEIMAN
mals shows a similar incidence of ovarian cysts in both groups. The percentage distribution of cysts of the other endocrine glands in these two groups
is also close enough to warrant the conclusion that some interrelationship exists
between the presence of certain hormones, benign breast tumors, and the
formation of cysts in the ovaries, pituitary, adrenals, and thyroid.
REFERENCE
HEIMAN,
J., AND KREBBIEL,0.F.: Am. J. Cancer 27 : 450, 1936.