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Estrogen deficiency reversibly induces telomere shortening in mouse granulosa cells and ovarian aging in vivo.
[aromatase deficiency]
Estrogen
is
implicated
as
playing
an
important
role
in
aging
and
tumorigenesis
of
estrogen
responsive
tissues
;
however
the
mechanisms
underlying
the
mitogenic
actions
of
estrogen
are
not
fully
understood
.
Here
we
report
that
estrogen
deficiency
in
mice
caused
by
targeted
disruption
of
the
aromatase
gene
results
in
a
significant
inhibition
of
telomerase
maintenance
of
telomeres
in
mouse
ovaries
in
a
tissue-
specific
manner
.
The
inhibition
entails
a
significant
shortening
of
telomeres
and
compromised
proliferation
in
the
follicular
granulosa
cell
compartment
of
ovary
.
Gene
expression
analysis
showed
decreased
levels
of
proto-oncogene
c-
Myc
and
the
telomerase
catalytic
subunit
,
telomerase
reverse
transcriptase
(
TERT
)
,
in
response
to
estrogen
deficiency
.
Estrogen
replacement
therapy
led
to
increases
in
TERT
gene
expression
,
telomerase
activity
,
telomere
length
and
ovarian
tissue
growth
,
thereby
reinstating
ovary
development
to
normal
in
four
weeks
.
Our
data
demonstrate
for
the
first
time
that
telomere
maintenance
is
the
primary
mechanism
mediating
the
mitogenic
effect
of
estrogen
on
ovarian
granulosa
cell
proliferation
by
upregulating
the
genes
of
c-
Myc
and
TERT
in
vivo
.
Estrogen
deficiency
or
over-activity
may
cause
ovarian
tissue
aging
or
tumorigenesis
,
respectively
,
through
estrogen
regulation
of
telomere
remodeling
.
Diseases
Validation
Diseases presenting
"first time"
symptom
achondroplasia
acute rheumatic fever
adrenal incidentaloma
adrenomyeloneuropathy
alpha-thalassemia
aniridia
aromatase deficiency
canavan disease
carcinoma of the gallbladder
cholangiocarcinoma
classical phenylketonuria
congenital adrenal hyperplasia
congenital toxoplasmosis
cowden syndrome
cushing syndrome
cutaneous mastocytosis
dedifferentiated liposarcoma
dentin dysplasia
dentinogenesis imperfecta
dracunculiasis
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
erdheim-chester disease
erythropoietic protoporphyria
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
fabry disease
familial mediterranean fever
gm1 gangliosidosis
harlequin ichthyosis
heparin-induced thrombocytopenia
hirschsprung disease
hodgkin lymphoma, classical
holt-oram syndrome
hydrocephalus with stenosis of the aqueduct of sylvius
junctional epidermolysis bullosa
kabuki syndrome
kallmann syndrome
liposarcoma
locked-in syndrome
lymphangioleiomyomatosis
malignant atrophic papulosis
megacystis-microcolon-intestinal hypoperistalsis syndrome
monosomy 21
neuralgic amyotrophy
oculocutaneous albinism
oligodontia
omenn syndrome
oral submucous fibrosis
papillon-lefèvre syndrome
pendred syndrome
phenylketonuria
primary effusion lymphoma
primary hyperoxaluria type 1
severe combined immunodeficiency
sneddon syndrome
triple a syndrome
trochlear dysplasia
von hippel-lindau disease
waldenström macroglobulinemia
well-differentiated liposarcoma
werner syndrome
wiskott-aldrich syndrome
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
zellweger syndrome
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