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Aromatase activity and bone homeostasis in men.
[aromatase deficiency]
It
is
known
that
sex
steroid
hormones
play
an
important
role
in
the
maintenance
of
bone
mass
in
males
as
well
as
in
females
.
Even
though
androgens
are
the
major
sex
steroids
in
men
,
their
primacy
in
regulating
male
skeletal
remodeling
has
been
increasingly
questioned
as
direct
and
indirect
evidence
emerged
suggesting
that
estrogens
may
also
play
a
major
role
in
male
skeletal
health
.
Recent
data
suggested
that
a
threshold
level
of
bioavailable
estradiol
is
needed
to
prevent
bone
loss
,
and
that
with
aging
an
increasing
percentage
of
elderly
men
begin
to
fall
below
this
level
.
The
testes
account
for
,
at
most
,
15
%
of
circulating
estrogens
in
the
male
;
the
remaining
85
%
comes
from
peripheral
aromatization
of
androgen
precursors
in
different
tissues
,
including
bone
.
Human
models
of
aromatase
deficiency
were
the
first
to
demonstrate
the
critical
importance
of
the
conversion
of
circulating
androgens
into
estrogen
in
regulating
male
skeletal
homeostasis
.
All
four
cases
of
aromatase-
deficient
men
reported
to
date
showed
an
identical
skeletal
phenotype
,
characterized
by
tall
stature
due
to
continued
longitudinal
growth
,
unfused
epiphyses
,
high
bone
turnover
,
and
osteopenia
.
Studies
using
knockout
mice
along
with
experimental
observations
in
rats
treated
with
an
aromatase
inhibitor
provided
useful
information
about
the
importance
of
aromatase
in
the
male
skeleton
.
Confirmatory
evidence
comes
from
recent
interventional
studies
in
adult
men
using
aromatase
inhibition
,
which
confirmed
that
estrogens
are
critically
important
to
the
male
skeleton
by
helping
to
control
rates
of
bone
remodeling
.
Intriguingly
,
common
polymorphisms
at
the
human
aromatase
(
CYP
19
)
gene
have
been
associated
with
differences
in
aromatase
activity
,
bone
turnover
,
and
rates
of
bone
loss
in
elderly
men
,
suggesting
that
variations
in
aromatase
efficiency
may
also
be
relevant
for
skeletal
homeostasis
.
Several
additional
mechanisms
have
been
proposed
in
which
aromatase
activity
could
be
modulated
under
certain
circumstances
in
different
tissues
.
Additional
studies
are
needed
to
identify
how
these
genetic
,
environmental
,
pathological
,
and
pharmacological
influences
might
modulate
aromatase
activity
in
vivo
,
increasing
or
reducing
estrogen
production
in
males
and
thereby
affecting
skeletal
health
.
Diseases
Validation
Diseases presenting
"bone remodeling"
symptom
aromatase deficiency
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