Cyclooxygenase 2 (Cox2) and Pain Management in Human Endometriosis

Abstract

Endometriosis is a chronic disease affecting approximately 6-10% of all women during their child-bearing ages worldwide. It is an estrogen-dependent disorder that manifests through chronic pelvic pain, dyspareunia, and infertility affecting 30-40% of women in the USA. Currently, surgical laparoscopy followed by histological classification remains the gold standard for diagnosis. Cyclooxygenase (COX; syn. Prostaglandin Endoperoxide Synthase, PGHS) is an enzyme that facilitates bioconversion of arachidonic acid (AA) to inflammatory prostaglandins (PGs). To date, three distinct isoforms have been identified namely, COX-1, COX-2 and COX-3. Regulation of COX-2 in endometrial epithelial and stromal cells by estrogens and/or progesterone or by hormone withdrawal is unresolved. Thus, in this study we aimed to analyze COX-2 protein levels in endometrial stromal and epithelial cells with and without hormones in vitro. To address this objective, primary endometriosis epithelial and stromal cells were stimulated with and without estrogen and progesterone hormones and afterwards the hormones were withdrawn and Prostaglandins (PG) secretion quantified. Results showed that treatment of both stromal and epithelial cells with estrogen and progesterone led to increased secretion of PGE2 and PGF2 while their withdrawal led to reduced secretion of the two prostaglandins. We observed that co-cultures of epithelial cells and stromal cells had a high secretion of PGE2 and PGF2 upon treatment of cells with both the two hormones compared to monocultures. This underscores the need for a model of co-cultures in attempting to understand the pathophysiology of pain generated during menstruation and endometriosis.