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Essential role for estrogen receptor beta in stromal-epithelial regulation of prostatic hyperplasia.
[aromatase deficiency]
Estrogens
,
acting
via
estrogen
receptors
(
ER
)
alpha
and
beta
,
exert
direct
and
indirect
actions
on
prostate
growth
and
differentiation
.
Previous
studies
using
animal
models
to
determine
the
role
of
ERbeta
in
the
prostate
have
been
problematic
because
the
centrally
mediated
response
to
estrogen
results
in
reduced
androgen
levels
and
prostatic
epithelial
regression
,
potentially
masking
any
direct
effects
via
ERbeta
.
This
study
overcomes
this
problem
by
using
the
estrogen-
deficient
aromatase
knockout
mouse
and
tissue
recombination
to
provide
new
insight
into
estrogen
action
on
prostate
growth
and
pathology
.
Homo-
and
heterotypic
aromatase
knockout
tissue
recombinants
revealed
stromal
aromatase
deficiency
induced
hyperplasia
in
normal
prostatic
epithelium
due
to
disruption
of
paracrine
interaction
between
stroma
and
epithelia
.
Treatment
of
tissue
recombinants
with
an
ERbeta-
specific
agonist
demonstrated
that
stimulation
of
ERbeta
elicits
antiproliferative
responses
in
epithelium
that
are
not
influenced
by
alterations
to
systemic
androgen
levels
or
the
activation
of
ERalpha
.
Additionally
,
work
performed
with
intact
aromatase
knockout
mice
demonstrated
that
the
administration
of
an
ERbeta-
specific
agonist
ablated
preexisting
prostatic
epithelial
hyperplasia
,
whereas
an
ERalpha-
specific
agonist
did
not
.
Therefore
,
failed
activation
of
ERbeta
,
resulting
from
local
stromal
aromatase
deficiency
,
in
conjunction
with
increased
androgen
levels
,
results
in
increased
epithelial
cell
proliferation
and
prostatic
hyperplasia
.
These
data
demonstrate
essential
and
beneficial
effects
of
estrogens
that
are
necessary
for
normal
growth
of
the
prostate
and
distinguishes
them
from
those
that
adversely
alter
prostate
growth
and
differentiation
.
This
highlights
the
potential
of
selective
estrogen-receptor
modulators
,
rather
than
aromatase
inhibitors
,
for
the
management
of
dysregulated
prostate
growth
.
Diseases
Validation
Diseases presenting
"tissue recombination to provide new insight into estrogen action on prostate growth and pathology"
symptom
aromatase deficiency
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