Inflammatory Status Influences Aromatase and Steroid Receptor Expression in Endometriosis

• Published in: Endocrinology (Philadelphia) 2008-03, Vol.149 (3), p.1190-1204
• Main Authors: Bukulmez, Orhan, Hardy, Daniel B, Carr, Bruce R, Word, R. Ann, Mendelson, Carole R
• Format: Article
• Language: English
• Subjects: Adult; Aromatase; Aromatase - metabolism; Biological and medical sciences; Biopsy; Case-Control Studies; Cross-Sectional Studies; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Endometriosis; Endometriosis - metabolism; Endometriosis - pathology; Endometrium; Endometrium - metabolism; Endometrium - pathology; Estrogen Receptor alpha - metabolism; Estrogen Receptor beta - metabolism; Estrogen receptors; Estrogens; Female; Female genital diseases; Fibroids; Fundamental and applied biological sciences. Psychology; Gene expression; Gynecology. Andrology. Obstetrics; Humans; Implants; Inflammation - metabolism; Medical sciences; mRNA; Non tumoral diseases; Ovary - metabolism; Peritoneum; Peritoneum - metabolism; Progesterone; Prospective Studies; Protein Isoforms - metabolism; Receptors; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; RNA, Messenger - metabolism; Up-regulation; Up-Regulation - physiology; Uterus; Vertebrates: endocrinology
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2007-0665

Aberrant up-regulation of aromatase in eutopic endometrium and implants from women with endometriosis has been reported. Aromatase induction may be mediated by increased cyclooxygenase-2 (COX-2). Recently, we demonstrated that progesterone receptor (PR)-A and PR-B serve an antiinflammatory role in the uterus by antagonizing nuclear factor κB activation and COX-2 expression. PR-C, which antagonizes PR-B, is up-regulated by inflammation. Although estrogen receptor α (ERα) is implicated in endometriosis, an antiinflammatory role of ERβ has been suggested. We examined stage-specific expression of aromatase, COX-2, ER, and PR isoform expression in eutopic endometrium, implants, peritoneum, and endometrioma samples from endometriosis patients. Endometrial and peritoneal biopsies were obtained from unaffected women and those with fibroids. Aromatase expression in eutopic endometrium from endometriosis patients was significantly increased compared with controls. Aromatase expression in endometriosis implants was markedly increased compared with eutopic endometrium. Aromatase mRNA levels were increased significantly in red implants relative to black implants and endometrioma cyst capsule. Moreover, COX-2 expression was increased in implants and in eutopic endometrium of women with endometriosis as compared with control endometrium. As observed for aromatase mRNA, the highest levels of COX-2 mRNA were found in red implants. The ratio of ERβ/ERα mRNA was significantly elevated in endometriomas compared with endometriosis implants and eutopic endometrium. Expression of PR-C mRNA relative to PR-A and PR-B mRNA was significantly increased in endometriomas compared with eutopic and control endometrium. PR-A protein was barely detectable in endometriomas. Thus, whereas PR-C may enhance disease progression, up-regulation of ERβ may play an antiinflammatory and opposing role.