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GPR30 deficiency causes increased bone mass, mineralization, and growth plate proliferative activity in male mice.
[aromatase deficiency]
Estrogen
regulation
of
the
male
skeleton
was
first
clearly
demonstrated
in
patients
with
aromatase
deficiency
or
a
mutation
in
the
ERα
gene
.
Estrogen
action
on
the
skeleton
is
thought
to
occur
mainly
through
the
action
of
the
nuclear
receptors
ER
α
and
ER
β
.
Recently
,
in
vitro
studies
have
shown
that
the
G
protein-coupled
receptor
GPR
3
0
is
a
functional
estrogen
receptor
(
ER
)
.
GPR
3
0
-
deficient
mouse
models
have
been
generated
to
study
the
in
vivo
function
of
this
protein
;
however
,
its
in
vivo
role
in
the
male
skeleton
remains
underexplored
.
We
have
characterized
size
,
body
composition
,
and
bone
mass
in
adult
male
Gpr
30
knockout
(
KO
)
mice
and
their
wild-
type
(
WT
)
littermates
.
Gpr
30
KO
mice
weighed
more
and
had
greater
nasal
-
anal
length
(
p
<
 
.
001
)
.
Both
lean
mass
and
percent
body
fat
were
increased
in
the
KO
mice
.
Femur
length
was
greater
in
Gpr
30
KO
mice
,
as
was
whole-body
,
spine
,
and
femoral
areal
bone
mineral
density
(
p
<
 
.
01
)
.
Gpr
30
KO
mice
showed
increased
trabecular
bone
volume
(
p
<
 
.
01
)
and
cortical
thickness
(
p
<
 
.
001
)
.
Mineralized
surface
was
increased
in
Gpr
30
KO
mice
(
p
<
 
.
05
)
.
Bromodeoxyuridine
(
BrdU
)
labeling
showed
greater
proliferation
in
the
growth
plate
of
Gpr
30
KO
mice
(
p
<
 
.
05
)
.
Under
osteogenic
culture
conditions
,
Gpr
30
KO
femoral
bone
marrow
cells
produced
fewer
alkaline
phosphatase-
positive
colonies
in
early
differentiating
osteoblast
cultures
but
showed
increased
mineralized
nodule
deposition
in
mature
osteoblast
cultures
.
Serum
insulin
-like
growth
factor
1
(
IGF-
1
)
levels
were
not
different
.
These
data
suggest
that
in
male
mice
,
GPR
3
0
action
contributes
to
regulation
of
bone
mass
,
size
,
and
microarchitecture
by
a
mechanism
that
does
not
require
changes
in
circulating
IGF-
1
.
Diseases
Validation
Diseases presenting
"functional estrogen receptor"
symptom
aromatase deficiency
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