close

Вход

Забыли?

вход по аккаунту

?

Mitotic activity in the thyroid gland of female rats.

код для вставкиСкачать
MITOTIC ACTIVITY I N T H E THYROID GLAND
O F FEMALE RATS1
THOMAS E. HUNT
Department of Anatomy, Uniaersity of Alabama
INTRODUCTION
The rate of mitotic cell division in certain organs has been shown
to vary with such factors as the phase of the estrous cycle, with age,
and with the time of day. This paper is concerned with the extent to
which these factors and especially the estrous cycle affect the rate of
division in the thyroid gland of the female rat. By using the rat it
will be possible to correlate the mitotic activity of the thyroid with that
of other structures which have already been studied (Hunt, '40, '42,
'43). Such a correlation is desirable since it would be helpful to know
whether a factor acts specifically on one organ or on a group of related
organs or whether it acts indirectly or not at all.
During the estrous cycle the mitotic activity varies markedly in a
number of organs. In the rat these include the ovaries (Lane and Davis,
'39), genital epithelia (Allen et al., '43), the hypophysis (Hunt, '42),
and adrenal gland (Hunt, '40). Some organs, however, such as the
intestine (Hunt, '42) are not affected and of those that are, not all have
have an increased activity at the same time. The genital epithelia and
the hypophysis have more mitoses at late estrus and the adrenal more
at diestrus. It thus appears that during the cycle the increased mitotic
activity in the various structures is due to more than one factor that
act in sequence.
I n order to evaluate the effect of the estrous cycle on mitotic activity
it is necessary to know the extent to which other factors such as age
and time of day affect the activity. In the hypophysis the increased activity at late estrus becomes markedly reduced as animals become
older (Hunt, '43) so that an animal of 300 days of age does not have
many more mitoses at late estrus than one of 100 days at diestrus. The
time of day at which an animal is killed is likewise an important factor
to be controlled, since in practically all organs where mitoses have been
studied there is an increased activity at one or more periods of the day.
'Aided by grants from the Jane Coffin Childs Memorial Fund f o r Medical Research and the
University of Alabama Research Fund.
133
134
THOMAS E. H U N T
Furthermore Blumenfeld (’42) has found that the periods of increased
activity are not the same for all structures of the same animal and he
concludes “that the factors which determine when and how often
mitosis occurs act on or reside within the organ as a unit”.
ACKNOWLEDGMENTS
I wish to thank Dr. C. M. Goss for supplying the rats from his colony
and for his helpful criticisms in the preparation of the paper.
MATERIALS AND METHODS
The 131 thyroid glands examined for mitotic activity were from the
same rats that supplied the hypophyses used in previous reports (Hunt,
’42, ’43). Tissue was fixed in Allen’s B-15 fluid and cleared in dioxan
after passing through alcohol from 10 to 70% in 10% steps. Sections
were cut at 3 micra and every tenth section was mounted and stained
according to Masson’s procedure. Four or five sections from each
gland were examined for mitotic figures. This represents an area approximating 12.5 sq. mm.
About half of the animals received colchicine 9 hours before being
killed. By halting division at the metaphase during this period the
mitotic count was approximately tripled and proved especially valuable
in the counts from the glands of older animals and in those killed in
diestrus where the mitotic figures were few and scattered. Animals
receiving colchicine were, with fourteen exceptions, killed between 4 and
5 P.M. Those not receiving it were killed between 11and 12 A.M.
The stages of the estrous cycle were determined by vaginal smears.
RESULTS
A definite correlation was found between the mitotic activity in the
thyroid gland and the sexual cycle. I n groups not receiving colchicine
and of comparable age, killed during each of the five phases of the
estrous cycle (groups 1-5. table l), there was a significantly higher
mitotic activity in the group killed in late estrus. Minimum activity
was found during proestrus and diestrus and an intermediate activity
occurred in early estrus and metestrus.
The variation at different phases was even more striking in the animals that received colchichine. Comparison of groups 6c, 7c, 9c, 12c,
and 13c (table l ) ,whi’ch were of comparable ages, shows that animals
killed in late estrus have by far the highest mitotic activity. The invariable low counts of animals killed in proestrus and diestrus in this
135
MITOTIC ACTIVITY I N THE THYROID
series is considered very significant since the use of colchicine rules
out the possibility of killing animals at a low ebb of mitotic activity that
might rise a few hours later. The intermediate activity in the early
estrous phase (group 7c) is not apparent in the animals that received
colchichine, because they were killed in the early part of the phase
whereas in the comparable group without colchicine some were killed
in the late part.
TABLE 1
Mitot% activity in the thyroid gland of groups of female rats with and without colchicine.
BmUP
~
*
NUMBEB
OF
ANIMALS
~~
1
2
3
4
5
6c
70
8c
9c
1oc
11e
12c
13c
~~
7
11
19
14
14
8
5
7
11
11
11
7
6
AQE, AVERAGE.
AND RANBE.
DAYS
STAQE OF
CYCLE W H E N
EILLrn
MITOSESPER
SQ. MM.
AVERAGE & 5. E.
Proestrus
Early estrus
Late estrus
Metestrus
Diestrus
Proestrus
Early estrus
Late estrus
Late estrus
Late estrus
Late estrus
Metestrus
Diestrus
0.35 -C 0.01
1.41 2 0.40
6.55 -C 1.07
1.37 -C 0.28
0.49 -C 0.12
1.09 -C 0.31
1.35 & 0.36
27.50 +- 9.87
12.60 -I: 3.31
9.10 2 1.75
4.25 ? 1.09
4.8 t 0.80
1.76 k 0.26
-~
103 ( 61-204)
87 ( 53-106)
85 ( 52-126)
94 ( 66-114)
87 ( 66-114)
126 ( 67-172)
121 ( 89-142)
85 ( 60-111)
132 (117-139)
150 (140-169)
206 (171-242)
135 (127-146)
113 ( 79-142)
There was considerable variation in the mitotic counts of the glands
of animals killed in late estrus. I n those not receiving colchicine this
ranged from 1.5 to 21.7 mitoses per square millimeter with five of the
nineteen animals having unusually low counts. The variability can be
explained in part by the variation in the time at which a maximum cell
division is attained. Most of the high counts were from animals killed
25 to 30 hours after cornified cells were first found in the vaginal smears,
but a few high counts were from animals killed 5 to 10 hours earlier.
Since the maximum activity is probably maintained for a few hours
only, it may very well have been missed in the animals with the low
counts. Thus, although there is undoubtedly individual variation, the
average mitotic count for animals in late estrus would be higher than
6.6 mitoses per square millimeter if all the animals had been killed at
a time of maximum mitotic activity.
The variability in mitotic activity associated with the age of the animal is shown by grouping according to age the forty animals receiving
Groups 6c-13c received colchicine 9 hours before death.
136
THOMAS E. HUNT
colchicine and killed in late estrus (groups 8c-llc, table 1).For the four
age groups the average mitoses per square millimeter was as follows :
A V E U Q E AQB, DAYS
85
132
150
206
MITOSES PER SQUARE MILLIMETER
27.5
12.6
9.1
4.25
I n a few individual cases older animals showed more mitoses than
younger ones, but the difference between the 55- and 206-day age groups
is highly significant statistically.
There was some evidence of a diurnal mitotic rhythm in the thyroid.
Of the twenty-two animals in groups 9c and 1Oc (table l), all of which
had received colchicine 9 hours before death, seven were killed at 11P.M.,
seven at 8 A.M., and eight at 5 P.M. The average mitoses per square millimeter for these was 19.6, 8.5, and 9.2, respectively. Although the difference between those killed at 11P.M. and 8 A.M. is apparently considerable
it is barely significant statistically (i.e., it might have been due to chance
in about once in twenty times). However, whether or not this may be
considered as evidence of a diurnal rhythm the fact remains that the
estrous cycle is effective in causing an increased activity regardless of
the time of day. It is interesting to note that in the hypophysis from
these same animals the highest mitotic activity also occurred in animals killed at 11P.M. (49 mitoses per sq. mm.) and the lowest in those
killed a t 8 A.M. (12.9 mitoses per sq. mm.).
Chouke and Blumenthal ( '42) found there are generally more mitoses
in the left lobe of the guinea pig thyroid than in the right lobe. This
does not seem to be true for the Eat. I n thirty-one glands, selected because more numerous mitoses were present and the orientation was
known, there were seventeen in which one side had more than 55% of
the mitoses (five had more than 60%). Of the seventeen, nine had more
on the left and eight, more on the right. The average mitoses per square
millimeter in all the right lobes was 13.2 and in the left 13. Such minor
differences can be accounted for by the errors in counting and are insignificant statistically.
The position of the dividing cells may have some bearing on the
problem of the origin of new follicles in the thyroid. The majority, or
65% of 1215 dividing cells recorded for this purpose touched the lumen
of the follicle and presumably replaced follicular cells that died. Most
of the others were separated from the lumen by at least one non-divicling cell and appeared to be the beginninq of a bud of a preexisting follicle. Very few divisions were seen in what might have been inter-
MITOTIC ACTIVITY IN THE THYROID
137
follicular cells, so that it seems unlikely that new follicles would arise
from them.
DISCUSSION
Since the greatest mitotic activity of the thyroid and hypophysis occurs in both glands during late estrus, it might be assumed that a single
factor is responsible for the activity. I n the thyroid, however, the increase and decrease in number of mitoses occurs somewhat earlier than
it does in the hypophysis. For example, an animal killed in early estrus
may show increased mitotic activity in the thyroid but not in the hypophysis. This suggests that the mitosis stimulating factor is not
necessarily the same for the two glands. Further support for such an
opinion has been obtained from experiments now in progress in which
injections of estrogens result in an increase in mitoses in the hypophysis
but not in the thyroid. It thus seems probable that the rise in mitotic
activity of the thyroid during the estrous cycle is not the direct result
of changes in the estrogen level but rather an indirect effect. That the
effect is indirect, working through the hypophysis, is suggested by the
work of Blumenthal and Loeb ('42) who found that administration of
an acid extract or implants of the hypophysis resulted in an increased
mitotic activity in the thyroid of the guinea pig.
During the estrous cycle in the guinea pig the time of highest mitotic
activity in the thyroid (Chouke et al., '35, '42) occurs in what corresponds t o the early part of diestrus in the rat. Since mitoses in the rat
were at a low level in diestrus, it is difficult to find an explanation that
accounts for the rise in both animals. The discrepancy, however, may
be more apparent than real and be due to the difference in the timing
of the phases of the estrous cycles in the two forms. There is also a
possibility that the mitotic activity is an expression of physiological
actions that occurred in the preceding cycle. Thus the factor that
causes the increased activity might be the same but requires different
lengths of time to become effective.
SUMMARY S N D CONCLUSIONS
The mitotic activity of the thyroid gland of the female rat varies with
the different phases of the estrous cycle. It is increased somewhat in
early estrus, attains a maximum in late estrus, declines in metestrus,
and is at a minimum in diestrus and proestrus. The maximum activity
does not quite correspond in time with that in the hypophysis but is
somewhat earlier. This and other evidence lead to the conclusion that
the increased mitotic activity in the thyroid is not due t o a direct effect
of an ovarian hormone but rather to an indirect effect.
138
THOMAS E. HUNT
As the animals advance in age to 200 days there is a decline in mitotic
activity so that the vqriation during the estrous cycle is hardly perceptible unless colchicine is given. There is some evidence of a diurnal
rhythm, since more mitoses were found in colchicine injected animals
killed at 11P.M. than in such animals killed at 8 A.M. or 5 P.M.
LITERATURE CITED
J. G. WILSONAND D. A. HESSION 1943 Differential growth in the
ALLEN,E., T. B. THOMAS,
ovaries and genital tract near the time of ovulation in rats treated with colchicine.
Am. J. Anat., vol. 72, pp. 291-337.
BLUMENFELD,
C. M. 1942 Normal and abnormal mitotic activity. I. Comparison of periodic
mitotic activity in epidermis, renal cortex, and submaxillary salivary gland of the
albino rat. Arch. Path., vol. 33, pp. 770-776.
BLUMENTHAL,
R. T., AND L. LOEB 1942 Parallelism i n the response of thyroid and parathyroid to various hormones and hormone-like substances. Endocrinology, vol. 30,
pp. 502-510.
CHOUKE,K. S., H. FRIEDMAN
AND L. LOEB 1935 Proliferative activity of the thyroid gland
of the female guinea pig during the sexual cycle. Anat. Rec., vol. 63, pp. 131-137.
CHOUKE,K. S., AND H. T. BLUMENTHAL
1942 Further investigations on the proliferative
activity of the thyroid gland of the guinea pig during the sexual cycle. Endocrinology, vol. 30, pp. 511-515.
HUNT,T. E. 1940 Mitotic activity of the adrenal gland of rats in different phases of the
sexual cycle. Anat. Rec., vol. 78, (Suppl.), p. 152.
1942 Mitotic activity in the anterior hypophysis of female rats. Anat. Rec., vol.
82, pp. 263-276.
1943 Mitotic activity in the anterior hypophysis of female rats of different age
groups and a t different periods of the day. Endocrinology, vol. 32, pp. 334-339.
LANE,C. E., AND F. R. DAVIS 1939 The ovary of the adult rat. I. Changes in growth of the
follicle and in volume and mitotic activity of the granulosa and theca during the
estrous cycle. Anat. Rec., vol. 73, pp. 4 2 9 4 4 2 .
Документ
Категория
Без категории
Просмотров
0
Размер файла
368 Кб
Теги
mitotic, gland, female, activity, thyroid, rats
1/--страниц
Пожаловаться на содержимое документа