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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
"bone mineral density"
symptom
achondroplasia
adrenal incidentaloma
allergic bronchopulmonary aspergillosis
aromatase deficiency
congenital adrenal hyperplasia
cushing syndrome
dentinogenesis imperfecta
erythropoietic protoporphyria
fabry disease
familial hypocalciuric hypercalcemia
familial mediterranean fever
kallmann syndrome
lamellar ichthyosis
phenylketonuria
primary hyperoxaluria type 1
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