Endometriosis is developing into a critical public health issue as patients incur total medical costs an average of 63% higher than healthy females. Approximately 10-20% of American women suffer from this disease, with 40% diagnosed infertile. Moreover, it is the most common gynecological cause of chronic pelvic pain [Merkin, D. et al, 2007]. Endometriosis is characterized by the growth of endometrial glands and stroma outside the normal lining of the uterine cavity. It is an exceptionally enigmatic disorder, as the etiology, pathophysiology, and pathogenesis are uncertain. Current therapies are inadequate as they merely manage symptoms without addressing the origin, incite adverse side effects, and are limited in their duration of use. In most cases, surgical options such as ablation of endometriotic lesions, bilateral salpingooophorectomy, and/or hysterectomy are required. Currently, endometriosis'is being diagnosed in younger women and manifesting with increased severity, thus an enhanced comprehension of this disorder as well as the development of safe and effective therapies is crucial. Endometriosis is an estrogen dependent disease, characterized by abnormal cholesterol metabolism and steroidogenesis. The peripheral benzodiazepine receptor (PBR) is the rate limiting molecule in the steroidogenic pathway. Pathologically, PBR plays a critical role in apoptosis, cell proliferation, impaired steroidogenesis, and aggressive phenotype. Our group has established that Ginkgo biloba (extract) downregulates PBR expression at both the protein and gene levels. We hypothesize that modulation of PBR by Gingko biloba may normalize cholesterol metabolism and steroid synthesis, thus reduce or reverse the development of eutopic and/or ectopic endometriosis lesions.
Our specific aims are as follows: 1) determine the contribution of PBR as a key molecular marker for the development, proliferation, and progression of endometriotic lesions using the K-ras knockout mouse model, and 2) determine the regulation of the cytostatic and growth-inhibitory effects of Gingko biloba on endometriosis in animal model. The long-term objective of this research plan is to propose a phytomedical approach to treating endometriosis by translating our findings from the bench to the clinic. This extremely novel research design is not only the first to examine the role of PBR in endometriosis, but also the foremost to propose Gingko biloba as a phytomedicinal therapeutic agent. ? ? ?