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Aromatase activity is absent in normal endometrium. In contrast, aromatase is expressed aberrantly in endometriosis, which gives rise to strikingly high levels of aromatase activity in this tissue. Both aromatase expression and activity are stimulated by PGE2. This results in local production of estrogen, which induces PGE2 formation and establishes a positive feedback cycle. Another abnormality in endometriosis, that is, deficient 17beta-HSD type 2 expression, impairs the inactivation of estradiol to estrone. These molecular aberrations collectively favor accumulation of increasing quantities of estradiol and PGE2 in endometriosis. The clinical relevance of these findings was exemplified by the successful treatment of an unusually aggressive case of postmenopausal endometriosis using an aromatase inhibitor.

Endometriosis is one of the most common causes of infertility and chronic pelvic pain and affects 1 in 10 women in the reproductive-age group. Although existence of this disease has been known for over 100 years, our current knowledge of its pathogenesis, the pathophysiology of related infertility, and its spontaneous evolution is limited. Several reasons contribute to our lack of knowledge, the most critical being the difficulty in carrying out objective long-term studies in women. Thus, we and others have developed the baboon as an appropriate nonhuman primate to study the etiology of this disease. We suggested that endometriosis develops in two distinct phases. Phase I is invasive and dependent on ovarian steroids. Phase II, which is the active phase of the disease, is characterized by endogenous estrogen biosynthesis. Following inoculation with menstrual endometrial tissues in two consecutive menstrual cycles, baboons develop lesions that are similar to those seen in humans. Laparoscopy at 1, 4, and 10 months revealed a preponderance of red raised nodules at the first month, while both red lesions and reddish-blue proliferative endometriotic lesions were evident at 4 and 10 months. The presence of glandular tissue and stromal fibroblasts in these lesions was confirmed by histology. Lesions obtained at 1 and 4 months expressed estrogen receptor beta (ERbeta), matrix metalloproteinase-7 (MMP-7), and vascular endothelial growth factor (VEGF) predominantly. However, aromatase expression was only readily evident at 10 months, although some lesions obtained at 4 months expressed low levels of aromatase. Therefore, our preliminary data suggest that endometriosis can be artificially induced in baboons, and the role of exogenous and endogenous estradiol in proliferation, angiogenesis, and immune modulations can now be evaluated in a potentially systemic manner.

Endometriotic cells contain the full complement of steroidogenic genes for de novo synthesis of estradiol from cholesterol, which is stimulated by PGE2 via enhanced binding of SF1 to promoters of StAR and aromatase genes in a synchronous fashion.