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Genital changes in female guinea pigs resulting from destruction of the median eminence.

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hstitute o f Neurology, Northwestern University Medioal S c l ~ o o l ,Clhicago, Illinois
In a recent publication (Dey, '43) the effects of various
hypothalamic and hypophysial lesions upon the gonadotrophic
activity of the pituitary of the female guinea pig were reported. The results of this study indicated that the median
eminence might be concerned in the regulation of pituitary
gonadotrophic functions, insofar as lesions that encroached
upon this structure abolished estrous cycles and caused genital atrophy.
In the present report, the effects of lesions placed directly
within the median eminence are presented.
Twenty-two mature female guinea pigs were utilized in this
study. Trial operations were first performed in order to determine the Horsley-Clarke coordinates upon which the
median eminence of the guinea pig lay. It was found that lesions located 8 to 9 mm. anterior to the interaural line and
situated at the base of the brain would cause considerable
damage to the median eminence. Lesions were placed in this
region in the twenty-two experimental animals. I n each animal three punctures were made in the brain, the first in the
midline and the other two 1 mm. to either side of the midline. An electrode was lowered a t each point until the base
'Aided by a grant from the Committee for Research i n Problems of Sex, National Research Council.
of the brain was reached and the lesions were made by passing 3 milliamperes of current for 30 seconds. Lesions made
in this manner usually fuse across the midline to form a single, large lesion.
Daily observations were made of the animals postoperatively and the condition of the vaginal membranes was recorded. The nature of the ovarian cycles was thus determined.
The animals that ran normal cycles postoperatively were
placed with males and observations were made for pregnancy.
The animals that became acyclic were observed for a t least 50
days and then the vaginal membranes were made to open
by injecting the animals with ovarian hormones. The animals
were injected with 100 i. u. of theelin2 in four consecutive
doses, on hours 0,24,48 and 60, followed by 0.2 i. u. of progesterone on hour 73. Following this artificial cycle, the animals were again observed for same 50 days before bein, sacrificed.
At the termination of the experiment the animals were
killed by a n overdosage of pentobarbital sodium and the
brains and ovaries were prepared for histological study by
our routine methods.
Of the twenty-two animals operated, seven ran normal cycles postoperatively. The fifteen remaining animals ceased
running cycles and their genitalia atrophied. After the vaginal membranes of these fifteen acyclic animals had been closed
for 50 days, they were opened artificially by the injection of
ovarian hormones. The membranes remained open for a normal interval, 3 days, and then closed again. Eleven of the fifteen animals continued to be acyclic following this procedure,
while the four remaining animals began to run regular, spontaneous cycles, and, after being placed with males, became
pregnant and delivered normally.
Received through the courtesy of the Parke, Davis & Company.
Receired through the courtesy of the Scliering Corporation.
The ovaries of the animals that ran normal cycles postoperatively and of those that regained normal cycles following the injection of ovarian hormones could not be distinguished from those of the normal animals. The ovaries of the
permanently acyclic animals were markedly atrophic and lacking in follicular development. They resembled those found in
the hypopliysectomized animal.
Fig. 1 Schematic reconstruction of mid-sagittal sections of the hypotlialainus
and hypophysis of the guinea pig upon which are projected various representative types of lesions encountered in this experiment. A, The lesions of the
permanently acyclic animals, with one exception, caused extensive damage t o the
median eminence; and, B, the lesion of the exceptional animal. C, The lesions
that only temporarily abolished estrous cycles caused but slight damage t o the
median eminence. D and E. Lesions t h a t had 110 effect upon estrous cycles lay
either rostra1 or caudal t o the median eminence. Ch., optic chiasma; C. KIL, nianimillary body; M. em., median eminence; P. d., pars distalis; P. int., pars intermedia; Pro., infundibular process; Stem, infundibular stem; V. 111, third
The brains of all the animals were examined microscopically. The lesions were found to vary somewhat in location
within the various groups, but, in general, there was some
correlation between the location of the lesion and the type
of postoperative activity displayed by the animals. The lesions
that permanently abolished estrous cycles, with one exception,
were located within the median eminence and destroyed a
major portion of that structure as shown in figure 1 A. The
lesion of the exceptional animal completely severed the hypophysical stalk, but caused only slight visible damage to the
median eminence itself (fig. 1 B). The lesions of the four
initially acyclic animals that regained cyclic activity following
the injection of ovarian hormones were more caudally placed
than those of the permanently acyclic group and consequently
caused only slight damage to the median eminence. In three
of the animals the main body of the lesion lay caudal to the
median eminence and destroyed only a small portion of the
caudal end of that structure (fig. 1 C), while in the fourth
animal, nearly all the caudal half of the median eminence was
destroyed. I n each animal the lesion completely severed the
hypophysial stalk.
The lesions that had no effect upon the sex cycle lay either
rostral (1 animal) or else caudal (6 animals) to the median
eminence. The anterior lesion injured only the rostral tip
of the median eminence as shown in figure 1 D, while the
caudal lesions caused no injury a t all to that structure although in the majority of cases they severed the hypophysial
stalk (fig. 1 E).
In previous investigations, we studied the effect of various
hypothalamic and hypophysial lesions upon the estrous cycles
of female guinea pigs (Dey, '43). Genital atrophy and loss
of ovarian cyclic activity occurred in only eleven animals although a large series of animals were studied. Information
gained from these studies indicated that destruction of the
median eminence or some closely related structure was re-
sponsible for the loss of estrous cycles that occurred in the
few animals.
In the present experiments, we attempted to place lesions
directly within the median eminence. The results of these experiments may be regarded as offering further support to the
suggestion that the median eminence plays an important role
in the control of the gonadotrophic functions of the anterior
pituitary. Destruction of a major portion of the median eminence invariably caused a cessation of sex cycles.
Four of the fifteen acyclic animals of the present series regained normal cyclic activity following the administration of a
“priming dose” of ovarian hormones. The damage to the
median eminence in these four animals was considerably less
than that seen in the eleven animals that remained permanently acyclic. The temporary loss of cycles in these animals
might be explained as follows: The initial functional damage
to the median eminence due to edema probably was much more
extensive than that later shown in the microscopic sections.
During this initial period of trauma, the hypophysis was deprived of whatever influence this area has upon it and failed to
secrete gonadotrophic hormones. When the edema of the median eminence later subsided the body was depleted of ovarian
hormones and consequently the initial stimulus for the release
of gonadotrophic hormones by the pituitary was lacking.
Therefore, normal cycles were not resumed. It is interesting
to note that once ovarian hormones were supplied, normal
cycles were immediately resumed and continued spontaneously until the animals were sacrificed a number of months
Dempsey (’39) demonstrated that normal sex cycles may
occur in the female guinea pig following transection of the
hypophysial stalk, and confirmation was provided by the findings of Leininger and Ranson ( ’43). Although normal cycles
did occur in a large number of the animals of these series,
yet both groups of investigators noted that a significant number of the experimental animals failed to run sex cycles following this procedure. It seems unlikely that the loss of sex
cycles in these cases was due to trauma to the pituitary gland
since it has been our experience as well as that of Burch and
co-workers (’37) that a large portion of the anterior lobe
(up to two-thirds of the entire gland in our experiments) may
be removed without abolishing sex cycles. It is likely that the
loss of sex cycles that frequently occurs after transection of
the pituitary stalk is due to injury to the median eminence.
Lesions placed in the region of the median eminence abolished estrous cycles in fifteen of twenty-two female guinea
pigs. Microscopic study of the brains showed that the major
portion of the median eminence was destroyed in fourteen of
the acyclic animals. The lesion of the exceptional animal transected the hypophysial stalk but caused only slight injury to
the median eminence itself. The lesions of the seven animals
that ran normal cycles postoperatively lay either rostra1 or
else caudal to the median eminence.
Four of the acyclic animals regained normal estrous cycles
following the injection of a “priming dose” of ovarian hormones. The damage to the median eminence in these four animals was considerably less than that seen in the permanently
acyclic group.
These results may be regarded as offering further support
to the theory that the median eminence plays an important
role in the control of the gonadotrophic functions of the anterior pituitary.
diagnosis and classification of menstrual disorders. J. A. M. A., vol.
108, pp. 96-100.
DEMPSBY,E. W. 1939 The relationship between the central nervous system and
the reproductive cycle in the female guinea pig. Am. J. Physiol., vol.
126, pp. 758-765.
DEY, F. L. 1943 Evidence of hypothalamic control of hypophysial gonadotrophic
functions in the female guinea pig. Endocrinology. I n press.
C. R., A N D S. W. RANSON 1943 The effect of hypophysial stalk
transection upon gonadotrophic function in the guinea pig. Anat. Rec.
In press.
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genital, pigs, guinea, destruction, change, eminence, female, media, resulting
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