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Aromatase deficiency inhibits the permeability transition in mouse liver mitochondria.
[aromatase deficiency]
Lack
of
estrogens
affects
male
physiology
in
a
number
of
ways
,
including
severe
changes
in
liver
metabolism
that
result
in
lipid
accumulation
and
massive
hepatic
steatosis
.
Here
we
investigated
whether
estrogen
deficiency
may
alter
the
functionality
and
permeability
properties
of
liver
mitochondria
using
,
as
an
experimental
model
,
aromatase
knockout
(
ArKO
)
male
mice
,
which
can
not
synthesize
endogenous
estrogens
due
to
a
disruption
of
the
Cyp
19
gene
.
Liver
mitochondria
isolated
from
ArKO
mice
displayed
increased
activity
of
the
mitochondrial
respiratory
complex
IV
compared
with
wild-
type
mice
and
were
less
prone
to
undergo
cyclosporin
A-
sensitive
mitochondrial
permeability
transition
(
MPT
)
induced
by
calcium
loading
.
The
altered
permeability
properties
of
the
mitochondrial
membranes
were
not
due
to
changes
in
reactive
oxygen
species
,
ATP
levels
,
or
mitochondrial
membrane
potential
but
were
associated
with
increased
content
of
the
phospholipid
cardiolipin
,
structural
component
of
the
mitochondrial
membranes
and
regulator
of
the
MPT
pore
,
and
with
increased
mitochondrial
protein
levels
of
Bcl-
2
and
the
adenine
nucleotide
translocator
(
ANT
)
,
regulator
and
component
of
the
MPT
pore
,
respectively
.
Real-time
RT-PCR
demonstrated
increased
mRNA
levels
for
Bcl-
2
and
ANT
2
but
not
for
the
ANT
1
isoform
in
ArKO
livers
.
Supplementation
of
17
beta
-estradiol
retrieved
ArKO
mice
from
massive
hepatic
steatosis
and
restored
mitochondrial
permeability
properties
,
cardiolipin
,
Bcl-
2
,
and
ANT
2
levels
.
Overall
,
our
findings
demonstrate
an
important
role
of
estrogens
in
the
modulation
of
hepatic
mitochondrial
function
and
permeability
properties
in
males
and
suggest
that
estrogen
deficiency
may
represent
a
novel
positive
regulator
of
Bcl-
2
and
ANT
2
proteins
,
two
inhibitors
of
MPT
occurrence
and
powerful
antiapoptotic
molecules
.
Diseases
Validation
Diseases presenting
"severe changes in liver"
symptom
aromatase deficiency
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