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ISSN:2171-6625
http://www.jneuro.comSeptember 18-19, 2017 | Dallas, USA
4
th
International Conference on
NEUROLOGY AND NEUROIMMUNOLOGY
Estrogens downregulate cyclo-oxygenase -2
(COX-2)
gene expression
Rosalie M Uht
1
and
Winfred Stacey
2
1
University of North Texas Health Science Center, USA
2
Center for Alzheimer’s and Neurodegenerative Disease Research, USA
I
nflammation plays a role in neurodegenerative illnesses
such as Alzheimer’s disease (AD). As a distinct fact, AD
predominates inpost-menopausal women as compared to aged
men. Together, these observations suggest that sex steroids
regulate neuro-inflammatory processes. Specifically, in the
premenopausal state, estrogens could have a protective effect
that would be lost after the menopause. To determine whether
estrogens could down-regulate an inflammatory process, an
amygdalar cell linewas used to determine the effect of estradiol
(E2) on cyclooxygenase–2
(COX-2)
gene expression. Estradiol
(E2) reduced
COX-2
mRNA and pre-mRNA levels. Given that
E2 exerts most of its known genomic effects by binding to two
estrogen receptors (ERs), ER-alpha (ER-a) and ER-beta (ER-b),
ER-aand -b selective ligandswereused todetermine the relative
contributions of the two receptors. ER-b accounted for all the
E2 repressive effect on
COX-2
RNA expression. Ligand-bound
ERs exert activating effects by binding to palindromic estrogen
response elements (EREs); however, repression may occur via a
different mechanism. The proximal
COX-2
gene promoter of the
COX-2
gene lacks an ERE, and E2 treatment leads to decreased
recruitment of the transcription factor NF-kB to the promoter.
E2 also leads to recruitment of histone deacetylase 1 and Sin3A,
members of a repressive complex. Lastly, E2 leads to increased
methylation of the
COX-2
proximal promoter. ER-b accounts for
some but not all of these effects. These data suggest that E2
has a neuroprotective effect by decreasing an inflammatory
response through pathways that are in part regulated by ER-b.
Speaker Biography
Rosalie M Uht was awarded her MD and PhD from the State University of New York
at Stony Brook in 1990. She did a combined Anatomic Pathology Residency and
Neuropathology Fellowship at the University of California, San Francisco (UCSF).
This was followed by Post-doctoral work as an NIH Clinical Investigator, also at UCSF.
She established her first independent laboratory at the University of Virginia at
Charlottesville in 2000. In 2008, she moved to UNTHSC where she established a second
independent lab and helped found the CANDR Brain Bank.
e:
rosalie.uht@unthsc.eduRosalie M Uht et al., J Neurol Neurosci, 8:5
DOI: 10.21767/2171-6625-C1-002