0013-7227/08/$15.00/0 Endocrinology 149(3):1190–1204 Printed in U.S.A. Copyright © 2008 by The Endocrine Society doi: 10.1210/en.2007-0665 Inflammatory Status Influences Aromatase and Steroid Receptor Expression in Endometriosis

ENDOMETRIOSIS IS AN estrogen-dependent disease associated with enhanced aromatase expression and local estrogen production in endometriotic tissues (1–3). Although retrograde menstruation with subsequent implantation and growth of endometrial cells within the peritoneal cavity is a widely accepted mechanism, multiple lines of evidence suggest that inflammation plays a critical role in the pathogenesis of this disease (4). This is supported by the fact that implanted endometriotic cells and intraperitoneal leukocytes produce proinflammatory cytokines creating a feed-forward regulatory loop in the development and progression of endometriosis (5). Estrogen synthesis from C19 steroids is catalyzed by aromatase P450, product of the aromatase/CYP19 gene. Human CYP19 is a single-copy gene expressed in a number of tissues, including placenta (6), gonads (7, 8), discrete nuclei of brain (9), adipose stromal cells (10, 11), and in breast cancer epithelial and stromal cells (12). Expression of aromatase in various tissues is controlled by tissue-specific promoters that lie upstream of tissue-specific first exons encoding the 5�-untranslated regions (UTRs) of aromatase mRNAs. These 5�-UTRs are spliced onto First Published Online November 29, 2007