Prostaglandins and COX-2
BY EDDIE MA
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.
Sources
Chishima F, Hayakawa S, Yamamoto T, Sugitani M, Karasaki-Suzuki M, Sugita K, Nemoto N. Expression of inducible microsomal prostaglandin e synthase in local lesions of endometriosis patients. Am J Reprod Immunol 2007;57(3):218-26.
Wu Y, Guo SW. Suppression of IL-1beta-induced COX-2 expression by trichostatin A (TSA) in human endometrial stromal cells. Eur J Obstet Gynecol Reprod Biol 2007 Feb 10; [Epub ahead of print]
