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The influence of thyroidectomy on the effectiveness of gonad stimulating hormones.

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THE INFLUENCE OF THYROIDECTOMY ON T H E
EFFECTIVENESS O F GONAD STIMULATING HORMONES
SAMUEL L. LEONARD AND IRA B. HANSEN
Biology Department, Union College, Schenectady, N e w P o r k
The importance of the relationship of the physiological
activity of the secretion of the thyroid gland to that of the
anterior pituitary caused us to undertake a study of the influence of thyroidectomy on the effectiveness of the gonad
stimulating hormones in the rat. Previous investigations of
this subject have led to controversial conclusions as a summary of the pertinent literature in chapter 15 of 'Sex and
Internal Secretions' indicates ( '32). Sehockaert ( '31) stated
that thyroidectomy increased the effectiveness of the pituitary sex hormones on the male accessory reproductive organs
in the rat. Smith and Engle ('30) obtained the greatest
response from pituitary implants in a thyroidectomized animal. Fluhman ('34) found that sheep pituitary extracts injected into completely or partially thyroidectomized rats
produced heavier ovaries than those in the unoperated controls whereas pregnancy blood serum extracts acted uniformly in both groups of animals.
We have studied the effect of thyroidectomy on the weights
of the accessory reproductive organs of male rats receiving
extracts of pregnancy mare serum (M.S.) and human pregnancy urine (P.U.). A similar study, though less extensive,
has been made on the females, confirming the work of Fluhman ( '34).
Aided by a grant from the National Iteseareh Council, Committee on Problems
of Sex.
203
THE ANATOMICAL RECORD, VOL. 64, NO. 2, AND BUPYLEMEJT N O . 2
204
SAMUEL L. LEONARD AND IRA B. HANSEN
EXPERIMENTAL PROCEDURE
Litter mate animals only were used in these experiments,
comparison being made within a litter group. The young
male rats were selected so that their body weights were fairly
uniform in the experimental and control groups and a t the
end of the experiment a comparison of the weights of the
reproductive organs in the operated and control injected animals was made. The operation was performed under a
binocular microscope and the completeness of the thyroid
removal was verified by a careful examination under the
microscope at autopsy. Little or no mortality occurred after
the method of operation was perfected.
The age of the rats varied from 26 to 48 days at the beginning of the experiment and no animal was older than
56 days at autopsy. I n certain of the experimental groups,
8 to 10 days lapsed after the operation before injections were
begun, while in others, injections were begun immediately.
I n some cases, the controls were subjected to a mock thyroidectomy in which some trauma was produced in the region
of the thyroid. As this control operation proved to have no
effect upon earlier experiments it was not attempted in later
cases. Weights of the gonads and accessory organs were
made on the day following the last injection.
The pregnancy mare serum extract2 was prepared according to the method of Meyer and Fevold ( '34),using 6 per cent
aqueous solution of N-butyl alcohol to extract the acetone
dried serum. Total doses equivalent to 50 to 100 mg. of dried
serum were injected. Antuitrin S3was used as the pregnancy
urine extract in doses of 0.2 to 0.25 cm. per day.
RESULTS
It is observed in tables 1 and 2 that thyroidectomy is without significant differential effect on the weights of the accessory reproductive organs of male rats injected with Antuitrin
"The acetone dried pregnant mare serum was obtained through the kindness
of Dr. A. E. Meyer, Ghappel Brothers, Rockford, Illinois.
*The Antuitrin 8 was given by Park, Davis & Co,, through the courtesy of
Dr. Oliver Kamm.
THYROIP-PITUITARY RELATIONSHIP
M:r
EXPEIU- N ~ M B E R
ORRATS
AVERAGEBODY
WEIGHT AT
AUTOPSY
(GUYS)
AVERAGE WEIGHT OF
ACCESSORY ORGANS
205
GROUP
PER CENT
PER CENT
DIFFERBNCE DIFFERENCE
OF GROUP
P B E 100 G X ,
RAT
(GRAMS)
-
Operated Control Operated
-___
45a
45b
45c
60
61
I
EXPEm.
"ZF
2
7
3
5
4
NUBfBER
OBRATS
73
57
45
58
97
I
84
73
58
67
113
I
AMRAGR 3ODY
WEIGHT AT
AUTOPSY
(GRAMS)
1.020
0.672
0.508
0.599
1.036
II
1
1.265
0.759
0.407
0.664
0.992
_
4
72
76
5
4
_
~
93
64
75
110
68
79
}
1
~
56.1
45.5
48.8
_
68.6
34.0
63.9
-6.1
18.0
4.4
AVERAGE WEIGHT OF
OVARIES
(GRAMS)
Operated Control Operated Control
_
67
I
-19.3
-11.4
24.8
- 9.7
$g:tc&
GROUP
PER CENT
PER CENT
DIFFERENCE DIFFERENOE
O F GROUP
PER 100 GM.
RAT
_
_
~
-18.2
33.8
-9.7
-23.61
\
~
3.2
_
_
_
206
SAMUEL L. LEONARD AND IRA B. HANSEN
variation in the weight of the accessory organs among the
control or thyroidectomized rats within a litter, as was found
when comparing the average of the accessory organ weights
of the controls with that of the operated animals. When the
average of several litters within a group is taken, the results
show very clearly that thyroidectomy does not enhance the
effeetiveness of these two gonad stimulating hormones
(column 8 of tables 1 and 2).
In thoss. animals in which the thyroid has been removed,
the body weights are almost always less than those of t,he
controls, although the animals at the end of the experiment
were in good health and gained weight during the treatment.
If calculations of the weights of the accessory or&
Oans are
made on the basis of a 100-$m. rat, the results are somewhat
differeni, as can be seen in the last column of the tables.
Since the operated animals were not as heavy as the controls,
it seems as if the weight of the accessory organs increases
in a greater proportion than in the controls and that thyroidectomy slightly favors the effectiveness of these gonad stimulating hormones. I n reality, however, the accessory organs
react independently of the body weight within certain limits.
Both pregnancy mare serum and Antuitrin S behave similarly whether they are administered immediately after thyroidectomy or after the lapse of several days. It was thought
that possibly a hypothyroid condition would be produced first
in those rats in which treatment was delayed, and this might
reveal a difference in the weight of the accessory glands.
However, the results are the same, no matter when treatment
is begun.
The testes of the rats of all groups were weighed, but it
was observed that there is no differential increase due to the
injections. It was noted in a few cases that the testicular
weight, when compared to that of the uninjected control, is
not increased by the treatment, which confirms an earlier
observation of Smith and Leonard ( '34).
I n the case of the females, table 2, the degree of enlargement of the ovaries is seen not to be influenced by thyroid
THYROID-PITUITARY RELATIONSHIP
207
removal. Neither does the comparison of the average uterine
weights of the experimental and control animals reveal any
significant differential effect. The uteri of the operated animals weigh, on the average, 4.2 per cent higher. These results
on the females concur with the findings of Fluhman (’34).
DISCUSSION
While it has been shown that a hyperthyroid condition in
the young rat decreases the effectiveness of gonad stimulating
hormones (Fluhman, ’34),the hypothyroid condition does not
always have the inverse effect. The results of these experiments quite definitely indicate that thyroid removal has no
effect on the gonad stimulating action of pregnancy urine
extract or pregnancy mare serum. At first glance, this seems
to reverse the findings of Smith and Engle ( ’30) and Schockaert (’31) in which thyroidectomy was found to enhance the
action of gonad stimulating substances. However, it must
be strongly emphasized that these workers used pituitary
implants or extracts of pituitary tissue which contained not
only the sex stimulating hormones but also hormones affecting other endocrine organs as well.
Fluhman (’34) is of the opinion that the thyroid activator
present in the pituitary extracts is sufficient to induce a degree of hyperthyroidism in the normal immature rat which
lessens the influence of the sex stimulating principle also
present. It is not within the scope of this paper to discuss
reasons for differences in the action of these two classes of
sex stimulating hormones. It is quite important to establish
that thyroidectomy has no influence on the effectiveness of
‘pure’ sex stimulating hormones. A ‘pure’ hormone in this
case means one free from principles which act directly on
other parts of the body; P.U. and M.S. influence the gonads
only.
It is interesting to note that although M.S. and P.U. act
similarly in the thyroidectomized rat, they show distinct differences in the hypophysectomized rat. M.S. completely
repairs the atrophy of the reproductive organs in the hy-
208
SAMUEL L. LEONARD AND IRA B. HANSEN
pophysectomized rat (Evans et al., ’33) ; P.U. fails to do this
(Smith and Leonard, ’34). I n this respect, M.S. has properties like pituitary gonad stimulating hormones.
Schockaert (’33) compared pituitary with urinary gonad
stimulating hormones quantitatively, in respect to their power
of stimulating the accessory organs of young male rats. He
determined the ‘genokinetic’ ratio N “by dividing the relative
change in weight of the accessory organs as compared to the
untreated control taken as unity, by the corresponding figure
for the testes weight” (weight being calculated on the basis
of 100 gm. of rat). On the average, he found this to be
N=1.22 to 1.27 for pituitary sex stimulating hormone, and
N =2.45 for urinary sex stimulating hormone (P.U.). The
weights of the reproductive organs of twenty rats in four
litters were used to determine the genokinetic ratio for mare
serum. This was found to be N=1.80. It so happens that
this ratio is approximately midway between the ratios for
the pituitary and the urinary preparations.
The results of these experiments are not difficult to interpret in view of the previous findings on thyroidectomy in
relation to the normal physiology of reproduction. Although
the amount of information on this point is small, the careful
work of Hammett (’26) and Smelser (’34) shows that removal of the thyroid has little influence on the reproductive
organs even after long periods of time. Smelser obtained
a slight decrease in the size of the reproductive organs after
a long period of time. I n the future, when ‘pure’ sex stimulating hormones are prepared from gland sources, it will be
interesting to see the effect of the removal of the thyroid
gland on the results obtained when these extracts are injected.
SUMMARY
Removal of the thyroid gland in young male or female rats
does not influence the effectiveness of extracts of pregnancy
urine or pregnancy mare serum even though the body weights
of the operated animals are less than the controls at the end
of the experiment.
THYROID--PITUITARY RELATIONSHIP
209
The genokinetic ratio N (Schockaert), which is an index
to the responsiveness of the reproductive organs of male rats
to sex stimulating hormones, was found to be N=1.80 for
pregnancy mare serum. This ratio is about half-way between
that obtained for the pituitary and the urinary (P.U.) sex
stimulating hormones.
LITER-4TURE CITED
EVANS,
H., K. MWEIGAND M. SIMPSON1933 Growth and gonad stimulating
hormones of the anterior hypophysis. Memoirs Univ. Calif. 11, chap. 6.
FLUHMAN,
C. F. 1934 The influence of the thyroid on the action of gonad
stimulating hormones. Am. J. Physiol., vol. 108, p. 498.
HAMMEW,
F. S. 1926 The role of the thyroid apparatus in the growth of the
reproductive system. Am. J. Physiol., vol. 77, p. 527.
AND H. L. Fwom 1934 Extraction of gonad stimulating substances
of anterior lobe of the hypophysis. Proc. SOLExp. Biol. and Med.,
vol. 31, p. 570.
SCRWAERT, J. A. 1931 Influence de la thyroidectomie sur la rbponse des
testicules e t du systhme genital secondaire male aux injections de
substances prehypophysaires chez le rat. Comp. Rend. SOC. Biol.,
T. 108, p. 431.
1933 Differences between anterior pituitary sex stimulating hormones and pregnancy urine substances as tested in the male mammal
and bird. Am. J. Physiol., vol. 105, p. 497.
SEX AND INTEaNaL SECRETIONS 1932 Williams and Wilkins co., Baltimore.
SMELSER,
G. K. 1934 Effect of thyroidectomy on testicular function. Anat.
hC., VOl. 60, SUppl., p. 53.
SMITH,P. E., AND E. T. ENGLE1930 Sex and Internal Secretions, p. 817.
Williams and Wilkina Go., Baltimore.
SMITH,P. E., AND 8. L. LEONARD1934 Response of the reproductive system
of hypophysectomized and normal rats to injections of pregnancy
urine. Anat. Rec., vol. 58, p. 145.
MEYER,A.,
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