Two recent studies focuses on the increased
role of prostaglandins and COX-2 in endometriosis
suggest a new class of drugs may be considered in
reducing the presence of prostaglandins in women with
endometriosis
A recent study conducted at the Department of Obstetrics
and Gynecology at the Nihon University School of Medicine
in Tokyo by Dr Chishima et al focuses on
a newly identified enzyme called microsomal human
prostaglandin E synthase (mPGES). This enzyme converts
prostaglandin H2 (PGH2) to prostaglandin E2 (PGE2).
In the non-patient, PGE2 is normally high only during
the luteal phase of the menstral cycle. This is the
phase where the endometrium is concerned with proliferating,
in preparation to receive an embryo after ovulation.
The present study was conducted to
determine if mPGES is present in abnormal levels in
the endometriotic tissues of patients with endometriosis.
Samples taken from the ectopic endometrium of seven
patients with endometriosis were examined for the expression
of mPGES. An increased expression of mPGES-1 messenger
RNA (mRNA) was discovered in the samples of ectopic
endometrium as compared with samples obtained from the
eutopic endometrium of non patients. The presence of
mPGES in the ectopic endometrium may increase the presence
of PGE2 in the endometrium.
The precursor of PGE2, PGH2 is produced
by cyclooxygenase-2 (COX-2). This enzyme is the topic
of another recent study conducted by Wu et al
at the Medical College of Wisconsin. Their study concerned
evaluating the possibility of using a drug called trichostatin
A (TSA) to halt the action of COX-2, reducing the levels
of PGE2 to halt the continued self proliferation of
ectopic endometriotic tissues.
Trichostatin A is a drug that falls
into the category of histone deacetylase inhibitors
(HDACIs) which work by interfering with the ability
of DNA to bind and coil around special DNA binding proteins
called histones.
Trichostatin A was found to suppress
the COX-2 gene and protein expression. This suppression
so far has only been demonstrated when COX-2 was induced
by interleukin-1ß, and only in endometrial stromal
cells. This finding suggests that HDACIs may be a new
class of drugs used to treat endometriosis by producing
the overall effect of reducing the presence of PGE2
in the ectopic endometriotic tissues.
Review by: Eddie
Ma
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