Studies in hereditary dwarfism in . mice VIII. The histology of the anterior pituitary of mice with hereditary adiposity and of dwarf mice with hereditary adiposity


Francis, T.

Acta Pathologica et Microbiologica Scandinavica 22: 138-143

1945


The anterior pituitary lobe of mice with a hereditary gene for adiposity and yellow coat is of a normal shape and size, and the anterior lobe parenchyma is normal of construction and composition. In the " fat. yellow dwarf mouse " the anterior pituitary lobe is hypoplastic, and the anterior lobe tissue is defective with predominance of small pyknotic acidophiles and chromophobes, just like in the " normal dwarf mouse " with no disposition to adiposity/yellow colour. Unlike the anterior lobe of the " normal dwarf " that of the " fat, yellow dwarf" contains a few hypoacidophiles and small typical acidophiles. The hypothesis is advanced that the gene for adiposity restrains the cycle and action of the pituitary lobe without causing observable morphologic changes in the anterior lobe of the normal mouse, whose cycle is stable.

(FROM
THE
UNIVERSITY
INSTITUTE
FOR
HUMAN
GENETICS,
COPENHAGEN. CHIEF:
TAGE
KEMP,
M.
D.)
STUDIES
IN
HEREDITARY
DWARFISM
IN
MICE
VIII*)
THE
HISTOLOGY
OF
THE
ANTERIOR
PITUITARY
OF
MICE
WITH
HEREDITARY
ADIPOSITY
AND
OF
DWARF
MICE
WITH
HEREDITARY
ADIPOSITY
By
Torben
Francis,
M.
D.
(Received
for
publication
December
22nd,
1944).
Hereditary
anterior
pituitary
dwarfism
in
mice
was
first
described
by
Snell
(1929),
and
the
anterior
pituitary
dwarf
mice
have
been
studied
closely
by
Smith
&
MacDowell
(1930,
1931),
Boettiger
&
Osborn
(1938),
Kemp
(1933,
1934,
1935,
1938),
Kemp
&
Marx
(1937),
Bartels
(1941),
Mollenbach
(1941),
Grunnet
(1942),
and
Francis
(1944).
The
gene
for
the
dwarfism
is
recessive,
and
the
dwarf
growth
is
due
to
hypoplasia
of
the
anterior
pituitary
lobe
(Smith
&
MacDowell
1930),
which
consists
almost
exclusively
of
small
pyknotic
acidophiles
and
small
pyknotic
chromophobes,
whereas
the
proper
hormone-pro-
ducing
cells,
the
typical
acidophiles,
are
totally
absent
(Francis
1944).
Hereditary
adiposity
in
mice
in
connection
with
a
gene
for
yellow
coat
has
been
found
by
Cuenot
(1905).
The
gene
determining
the
yellow
colour
is
dominant
with
a
recessive
lethal
effect,
so
that
the
mice
that
are
homozygous
for
the
yellow
colour
die
early
in
the
fetal
period,
while
of
the
offspring
of
2
heterozygous
mice
1
/
3
will
become
grey
and
2/3
yellow.
Gradually
the
yellow
mice
will
develop
adiposity
as
well
attaining
a
weight
of
70
to
80
gm
(normal
mice
about
30
gm).
The
increase
in
weight
is
in
particular
due
to
large
deposits
of
fat.
At
experiments
of
parabiosis
between
a
normal
mouse
and
a
fat
mouse
both
mice
become
normal.
This
fact
is
indicative
that
the
cause
of
the
adiposity
is
of
a
hormonal
character
(Weitze
1940).
A
histologic
examination
of
the
anterior
pituitary
lobe
of
the
fat
mouse
has
shown
nothing
abnormal
(Weitze
1940,
in
collaboration
with
Bj.
Vimtrup).
*)
Previous
publications
in
this
series:
Acta
path.
et
microbial.
stand.
XIII,
512,
36
XIV,
197,
37
Suppl.
XXXVII,
290,
38
XVIII,
20,
41
XIX,
563,
42
XXI,
928,
44
XXI,
945,
44.
139
A
summation
of
the
genes
for
anterior
pituitary
dwarfism
and
adiposity/yellow
coat
has
been
undertaken
by
Kemp
(1943),
who
mated
mice
that
were
heterozygous
for
dwarfism
with
fat
yellow
mice
and
in
the
breed
got
fat
yellow
mice
with
a
heterozygous
gene
for
anterior
pituitary
dwarfism.
By
intermating
of
fat
yellow
mice
hetero-
zygous
for
dwarfism
2/16
of
the
offspring
were
yellow
dwarfs,
which
gradually
became
fat
weighing
from
10
to
20
gm
(the
average
weight
of
dwarfs
with
no
disposition
to
adiposity
about
9.7
gin).
The
anterior
lobe
of
the
pituitary
of
the
anterior
pituitary
dwarf
mouse
is
according
to
Francis
(1944)
subject
to
peculiar
proportional
changes
in
the
number
of
glandular
cells.
The
number
of
small
pykno-
tic
acidophiles
and
chromophobes
is
greatly
increased,
so
that
they
dominate
the
picture
completely,
whereas
hypoacidophiles,
typical
acidophiles,
and
large
acidophiles
i.
e.
the
proper
hormone-produc-
ing
element
are
absent.
Of
typical
chromophobes
only
a
very
small
number
are
found.
Francis
takes
this
parenchyma
change
to
be
ex-
pressive
of
an
abnormally
fast
cell
cycle
(»a
proportional
change
to
the
right
in
the
cell
picture«).
The
nuclei
of
the
glandular
cells,
which
normally
do
not
become
pyknotic
and
decay
till
after
the
glandular
cells
from
the
chromophobe
stage
have
passed
by
the
hypoacidophilic
and
typical
acidophilic
stages,
begin
in
the
dwarf
mouse
to
decay
(become
pyknotic)
already
at
the
point
of
time
at
which
the
chromo-
phobe
mother
cell
is
about
to
begin
acting
as
a
glandular
cell
(become
acidophilic).
This
early
decay
of
the
glandular
cells
is
regarded
as
the
cause
of
the
insufficient
but
not
quite
stopped
action
of
the
anterior
pituitary
lobe
of
the
dwarf
mouse.
Francis
(1944)
has
shown
that
the
anterior
pituitary
lobe
of
the
anterior
pituitary
dwarf
mouse
is
far
more
susceptible
to
sex
hormones
than
that
of
the
normal
mouse,
since
the
anterior
pituitary
lobe
of
the
dwarf
is
transformed
into
a
chromophobe
adenoma
already
after
a
very
short
period
of
treatment,
whereas
the
anterior
lobe
of
the
normal
mouse
has
hardly
undergone
any
change
in
appearance
after
the
same
dose
and
period
of
treatment.
The
influence
of
the
sex
hor-
mones
on
the
anterior
pituitary
lobe
seems
to
consist
in
a
checking
of
the
cell
cycle
with
»a
proportional
change
to
the
left
in
the
cell
picture«.
Weitze's
experiments
of
parabiosis
suggested
that
the
cause
of
the
adiposity
of
the
fat
mouse
is
hormonal
disturbances,
whereas
the
histologic
anterior
lobe
examination
showed
nothing
abnormal.
If
we
take
it
for
granted
that
the
normal
anterior
pituitary
lobe
has
a
stable
cycle,
which
is
very
insusceptible
to
hormonal
disturbances
in
relation
to
that
of
the
dwarf
mouse,
then
it
seems
natural
to
presume
that
a
hormonal
disturbance,
which
does
not
in
itself
give
rise
to
morphologic
changes
in
the
»normal«
anterior
pituitary
lobe,
might
act
on
and
alter
the
rather
unstable
cycle
in
the
anterior
lobe
of
the
dwarf
mouse.
In
order
to
throw
a
light
on
this
question
the
140
author
has
examined
the
anterior
pituitary
lobe
of
2
grey
mice
(i.
e.
normal
mice)
200
and
278
days
old
respectively,
of
7
yellow
mice
between
the
ages
of
62
and
279
days
(3
young,
yellow
mice,
4
rather
old,
yellow,
fat
mice),
and
of
2
yellow,
fat
dwarf
mice
300
and
372
days
old
respectively.
Technique.
The
histologic
technique
has
been
described
in
previous
works,
to
which
is
referred.
Fixation:
Helly.
Staining:
Hematoxylin-
picroeosin.
Observations.
In
the
yellow
mice
and
the
yellow/fat
mice
without
anterior
pituitary
dwarf
growth
there
are
found
no
cellular
changes.
This
is
in
conformity
with
Weitze
&
Vinztrup's
description
of
the
anterior
pituitary
lobe
of
the
fat,
yellow
mouse.
The
anterior
lobe
parenchyma
of
the
fat,
yellow
mouse
corresponds
in
its
composition
exactly
to
that
of
the
normal,
grey
mouse
(table
1).
In
the
2
fat,
yellow
dwarfs
the
shape
and
size
of
the
pituitary
body
is
exactly
like
that
of
the
anterior
pituitary
dwarf
mouse
with
no
disposition
to
yellow
colour/adiposity.
The
anterior
lobe
parenchyma
corresponds
likewise
in
all
great
essentials
to
that
of
the
dwarf
with
no
disposition
to
yellow
colour/adiposity,
with
pronounced
pre-
dominance
of
small
pyknotic
acidophiles
and
small
pyknotic
chromo-
phobes.
But
unlike
the
anterior
lobe
tissue
of
the
»normal
dwarfs«
that
of
the
»fat
dwarfs«
contains,
besides,
a
few
hypoacidophiles
and
typical
acidophiles.
These
cells
are
somewhat
smaller
than
the
cor-
responding
cells
in
the
normal
mice
but
they
have
a
distinctly
acido-
philic,
slightly
granulated
cytoplasm,
distinct
cell
boundaries,
and
sometimes
a
suggestion
of
a
Golgi
zone.
Discussion.
The
observation
in
the
anterior
pituitary
lobe
of
the
»fat
dwarf«
of
hypoacidophiles
and
small
typical
acidophiles,
which
never
occur
in
that
of
the
»normal
dwarf«
when
the
latter
is
more
than
7
weeks
old,
is
peculiar.
According
to
the
author's
hypothesis
the
»normal
dwarf
mouse«
has
an
incomplete,
abnormally
fast
cell
cycle.
The
findings
are
indicative
that
the
cycle
of
the
»fat
dwarf«
is
subject
to
a
slight
checking
or
restraining
allowing
of
the
formation
of
the
few
hypoacidophiles
and
typical
acidophilees,
i.
e.
a
step
in
the
direction
of
the
normal
cycle.
This
is
suggestive
of
the
fact
that
the
anterior
pituitary
lobe
of
the
fat
mouse
is
under
the
influence
of
a
factor
that
has
a
restraining
effect
on
the
cycle
and
action
without,
however,
giving
rise
to
observable
morphologic
changes.
Table
1.
The
glandular
cells
of
the
anterior
pituitary
lobe
of
yellow
fat
mice
and
of
yellow
fat
dwarf
mice.
Normal
mouse
(control)
Grey
mice
(normal
mice)
Yellow
fat
mice
Dwarf
mouse
(control)
Yellow
fat
dwarf
mice
No.
240
F
3
F
2
F
11
F
39
F
46
F
25
F
41
F
30
F
1
275
569
568
Age
(Days)
25
230
278
62 62 62
103
116
131
279
273
300
372
Sex
(d
=male,
9
--female)
9
9
d'
c3'
d'
d'
d'
d'
c3'
d'
d
d'
d'
Weight
(in
gm)
12,2
21,5
24,5
19,0
19,5
22,5
39,0
41,9
30,5
45,0
9,8
8,5
15,0
Anterior
lobe
cells
Typical
chromophobes
-
i
--
i
-
++ ++ ++ ++ ++ ++ ++ ++ ++
(+)
(+)
(+)
Hypoacidophiles
(+)
(
-
0
(+) (+)
(+)
(+)
(+) (+)
(+)
(+)
0
(+)
(+)
Typical
acidophiles
+++ +++ +++
+++
4++
+++
+++ +++
+++
+++
0
(+)
CO
Large
acidophiles
(+)
(+)
(+)
(+)
(+)
(+)
(-)-)
(+)
(4
-
)
(
-
0
0
0
0
Hyperacidophiles
CO
(+)
(+)
(+)
(+)
(4
-
)
(+)
(+) (+)
(+) (+)
(+)
(+)
Small
pyknotic
acidophiles
(+)
(+)
(+) (+) (+)
(1-)
(+)
(+)
(+)
(+)
++++ +++ +++
Small
pyknotic
chromophobes
(+)
(+)
(
-
I
-
)
(+)
(+) (+)
(+)
(
-
0
(+)
(+)
++++
+ -
HI
-
+++
Basophiles
0
0
0
0
0
0
0
0
0
0
0
0
0
+
+
+
+
the
total
number
++++
the
great
majority
±+±
numerous
++
many
some
(scattered
in
the
field
of
vision)
(+)
a
few
0
none
142
Table
I.
The
glandular
cells
of
the
anterior
pituitary
of
a
normal
mouse,
a
yellow
fat
mouse,
a
dwarf
mouse
and
a
yellow
fat
dwarf
mouse.
%sr
IF
111
44111
ID
ollb
1,..7:
11110
1
r
a
No
240.
Normal
mouse.
b
No
F
30.
Yellow
fat
mouse.
c
No
273.
Dwarf
mouse.
d
No
569.
Yellow
fat
dwarf
mouse.
Hematoxylin-eosin.
Magnified
1000
X.
143
Summary.
The
anterior
pituitary
lobe
of
mice
with
a
hereditary
gene
for
adiposity
and
yellow
coat
is
of
a
normal
shape
and
size,
and
the
anterior
lobe
parenchyma
is
normal
.
of
construction
and
com-
position.
In
the
»fat,
yellow
dwarf
mouse«
the
anterior
pituitary
lobe
is
hypoplastic,
and
the
anterior
lobe
tissue
is
defective
with
pre-
dominance
of
small
pyknotic
acidophiles
and
chromophobes,
just
like
in
the
»normal
dwarf
mousex
with
no
disposition
to
adiposity/yellow
colour.
Unlike
the
anterior
lobe
of
the
»normal
dwarf
that
of
the
»fat,
yellow
dwarf«
contains
a
few
hypoacidophiles
and
small
typical
acidophiles.
The
hypothesis
is
advanced
that
the
gene
for
adiposity
restrains
the
cycle
and
action
of
the
anterior
pituitary
lobe
without
causing
observable
morphologic
changes
in
the
anterior
lobe
of
the
normal
mouse,
whose
cycle
is
stable.
LITERATURE:
Bartels,
E.
D.:
Acta
path.
et
microbiol.
Scand.
XVIII,
20,
1941.
Cuenot,
L.:
Arch.
Zool.
Exp.
et
Gen.
1905.
Francis,
T.:
The
development
of
the
pituitary
at
hereditary
anterior
pituitary
dwarfism
in
mice.
Munksgaard.
Kopenhagen
1944.
Acta
path.
et
microbiol.
Scand.
XXI,
928,
44
XXI,
945,
44.
Grunnet,
J.:
Acta
path.
et
microbiol.
Scand.
XIX,
563,
1942.
Kemp,
T.:
Acta
path.
et
microbiol.
Scand.
Suppl.
16,
189,
1933.
Hereditas
XXIX,
76,
1943.
Weitze,
M.:
Hereditary
adiposity
in
mice
and
the
cause
of
this
anomaly.
pp.
96.
Copenhagen
1941.