MON-026 Estradiol Triggering Extracellular Matrix Degradation Leading Signalling Cascades Succeeding a Feedback Loop as Contributing Factor to Develop Endometriosis in Females of Reproductive Age

Abstract INTRODUCTION: Endometriosis is common gynaecological disorder that leads to infertility in females of reproductive age. It is characterized by endometrial glands and stromal tissues outside the wall of uterus. Upregulation of estradiol is responsible for the cell proliferation, adhesion and invasion in endometriosis. It enhances prostaglandins (PGE-2) that triggers the formation of matrix metalloproteinases (MMPs), Tumor necrosis factor-α (TNF-α) and nuclear factor kappa B (NF-kB). Whereas, levels of progesterone are reported to be decreased in the patients with endometriosis. Less production of progesterone activity of 17β-hydroxysteroid dehydrogenase-II (17β-HSD-II) decreases that converts estradiol to less potent estrone. Intake of excess trans-fats and deficiency of vitamin D raises level of arachidonic acid and converts PGE-2 by the action cyclooxygenase (COX-2). PGE2 in theca cells of ovaries increases cAMP and activity of liver receptor homologue-1/steroidogenic factor-1(LRH-1/SF-1) thus leading to the stimulation of aromatase enzyme. MATERIALS AND METHODS: Two hundred eighty-eight (n=288) females with endometriosis and hundred (n=100) controls were enrolled. Informed consent was obtained before the collection of samples. Levels of estradiol, progesterone, aromatase enzymes, 17β-HSD-II, COX-2, PGE-2, MMPs (2, 7, 9), vitamin D and lipopolysaccharides (LPO) were estimated by respective protocols. RESULTS: Findings suggests significant increase in the levels of estradiol, aromatase enzymes, COX-2, PGE-2, MMPs (2,7,9) and LPO (67.08±5.55 pg/ml, 7.16±1.28 ng/ml, 1.56±0.144 ng/ml, 4.89±0.61 pg/ml, 995.2±8.15 ng/ml, 105.2±7.19 ng/ml, 109.2±12.25 ng/ml and 125.25±11.26 pg/ml) in patients as compared to (21.08±3.65 pg/ml, 2.08±0.15 ng/ml, 0.61±0.056 ng/ml, 1.158±0.18 pg/ml, 388.26±14.26 ng/ml, 66.29±5.26 ng/ml, 38.29±15.2 ng/ml and 17.25±1.26 pg/ml) controls respectively. Whereas, levels of progesterone, 17β-HSD-II and vitamin D remained significantly low in the endometrial patients (3.07±1.08 ng/ml, 0.183±0.024 ng/ml and 17.17±2.3 ng/ml) as compared to healthy females (29.22±3.29 ng/ml, 1.43±0.153 ng/ml and 36.26±3.09 ng/ml). CONCLUSION: Current study suggests the role of estradiol in triggering ECM degradation and initiating signalling cascades that following a feedback loop enhances the levels of estradiol and contributes in the development and progression of endometriosis. Hence, therapies with supplementation of vitamin D and progesterone may help in regressing the role estradiol and other contributing factors that are involved in the development and progression of endometriosis in the patients. Keyword: Endometrial glands, Stromal tissues, Estrogen, Progesterone, Endometriosis, Vitamin D