| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Starzinski-powitz, Anna Banu, Sakhila K. Lee, Jehoon Balasubbramanian, Dakshnapriya Burghardt, Robert C. Arosh, Joe A. Stanley, Jone A. Long, Charles R. Meagher, Mary W. Osteen, Kevin G. Bruner-tran, Kaylon L. |
| Description |
Author Affiliation: Arosh JA ( Department of Integrative Biosciences, Texas A&M University, College Station, TX 77843); Lee J ( Department of Integrative Biosciences, Texas A&M University, College Station, TX 77843); Balasubbramanian D ( Department of Integrative Biosciences, Texas A&M University, College Station, TX 77843); Stanley JA ( Department of Integrative Biosciences, Texas A&M University, College Station, TX 77843); Long CR ( Department of Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843); Meagher MW ( Department of Psychology, College of Liberal Arts, Texas A&M University, College Station, TX 77843); Osteen KG ( Department of Obstetrics and Gynecology, Vanderbilt University School of Medicine, Nashville, TN 37232); Bruner-Tran KL ( Department of Obstetrics and Gynecology, Vanderbilt University School of Medicine, Nashville, TN 37232); Burghardt RC ( Department of Integrative Biosciences, Texas A&M University, College Station, TX 77843); Starzinski-Powitz A ( Biosciences, Molecular Cell Biology and Human Genetics, Goethe University, Frankfurt am Main 60483, Germany.); Banu SK ( Department of Integrative Biosciences, Texas A&M University, College Station, TX 77843); |
| Abstract |
Endometriosis is a debilitating, estrogen-dependent, progesterone-resistant, inflammatory gynecological disease of reproductive age women. Two major clinical symptoms of endometriosis are chronic intolerable pelvic pain and subfertility or infertility, which profoundly affect the quality of life in women. Current hormonal therapies to induce a hypoestrogenic state are unsuccessful because of undesirable side effects, reproductive health concerns, and failure to prevent recurrence of disease. There is a fundamental need to identify nonestrogen or nonsteroidal targets for the treatment of endometriosis. Peritoneal fluid concentrations of prostaglandin E2 (PGE2) are higher in women with endometriosis, and this increased PGE2 plays important role in survival and growth of endometriosis lesions. The objective of the present study was to determine the effects of pharmacological inhibition of PGE2 receptors, EP2 and EP4, on molecular and cellular aspects of the pathogenesis of endometriosis and associated clinical symptoms. Using human fluorescent endometriotic cell lines and chimeric mouse model as preclinical testing platform, our results, to our knowledge for the first time, indicate that selective inhibition of EP2/EP4: (i) decreases growth and survival of endometriosis lesions; (ii) decreases angiogenesis and innervation of endometriosis lesions; (iii) suppresses proinflammatory state of dorsal root ganglia neurons to decrease pelvic pain; (iv) decreases proinflammatory, estrogen-dominant, and progesterone-resistant molecular environment of the endometrium and endometriosis lesions; and (v) restores endometrial functional receptivity through multiple mechanisms. Our novel findings provide a molecular and preclinical basis to formulate long-term nonestrogen or nonsteroidal therapy for endometriosis. |
| ISSN |
00278424 |
| e-ISSN |
10916490 |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number |
31 |
| Volume Number |
112 |
| Language |
English |
| Publisher |
National Academy of Sciences |
| Publisher Date |
2015-08-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Endometriosis Drug Therapy Pathology Receptors, Prostaglandin E, EP2 Subtype Antagonists & Inhibitors Receptors, Prostaglandin E, EP4 Subtype Animals Apoptosis Drug Effects Biphenyl Compounds Pharmacology Therapeutic Use Caspase 3 Metabolism Cell Line Cell Movement Cell Survival Disease Models, Animal Endometrium Blood Supply Estrogens Biosynthesis Inflammation Mice Neovascularization, Pathologic Pelvic Pain Poly(ADP-ribose) Polymerases Progesterone Signal Transduction Steroids Xanthones Research Support, N.I.H., Extramural Multidisciplinary |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Multidisciplinary |
