Development of osteoporosis and obesity in ovariectomized estrogen receptor β knock out and wild type mice.
Tác giả: D.Seidlová-Wuttke1, T. Vortherms1, N.B. Tiep1, J.A. Gustafsson2, W. Wuttke1.
(1) Dept. of Endocrinology University of Goettingen, Germany ; (2) Dept. of Medical Nutrition and Dept. of Bioscience Karolinska Institute, Huddinge, Sweden.
The
4th
Meetting
of
CASCADE
-
Chemicals
as
Contaminants
in
the
food
chain
(Network
of
Excellence
for
Research,
Risk
Assessment
and
Education)
-
Brussels,
Belgium,
May
2008.
Estrogen
receptor
β
knock
out
(BERKO)
mice
have
been
amply
used
to
study
the
function
of
the
estrogen
receptor
of
the
beta
subtype
(ERβ).
A
relatively
inconspicuous
body
weight
and
bone
phenotype
as
well
as
little
effects
of
short
term
ovariectomy
(ovx)
has
been
reported.
Long
lasting
studies
on
the
bone
phenotype
of
intact
and
ovx
mice
are
lacking.
Utilizing
quantitative
computer
tomography
(qCT)
we
therefore
determined
mineral
densities
of
the
cancellous
and
cortical
bone
of
the
metaphysis
of
the
tibia
as
well
as
their
respective
sizes,
in
intact
and
ovx
BERKO
mice
and
compared
the
data
with
those
determined
in
wild
type
(WT)
animals.
In
addition,
the
development
of
body
weights
(BW)
of
a
paratibially
located,
estrogen
regulated
fat
depot
was
studied.
Animals
were
ovx
at
3
months
of
age
and
qCT
analysis
performed
in
2-4
months
intervals
until
12
months
of
age,
i.e.
until
9
months
after
ovx.
There
were
few
significant
differences
in
development
of
BW,
size
of
fat
depots,
trabecular
and
cortical
desities
as
well
as
of
their
areas
observed
in
the
intact
BERKO
animals
as
compared
to
the
intact
WT
mice.
Following
ovx,
however,
marked
differences
were
unmarked.
OVX
WT
animals
gained
BW
and
had
increased
size
of
the
fat
depot
within
2
months
after
ovx
while
such
obesity
developed
much
later
in
the
ovx
BERKO
mice.
At
months
7
and
9
after
ovx,
BERKO
mice
were
significantly
heavier
than
the
respective
WT
mice.
Similar
differences
in
development
of
osteoporosis
could
be
demonstrated,
i.e.
ovx
WT
animals
lost
trabecular
density
more
rapidly
than
the
BERKO
mice
which
caught
up
however,
7
months
after
ovx
and
later.
Similar
effects
could
be
determined
for
the
cortical
parameters.
It is concluded that the absence of ERβ in ovx BERKO animals during the first 3-5 months following ovx had protective effects against obesity and osteoporosis which, however, vanished at later time points. The molecular mechanisms of this late "normalization" of ovx induced effects in BERKO remain to be determined.
