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13. Prostaglandin E2 via Steroidogenic Factor-1 Coordinately Regulates Transcription of Steroidogenic Genes Necessary for Estrogen Synthesis in Endometriosis

Author

Attar, Erkut, primary, Tokunaga, Hideki, additional, Imir, Gonca, additional, Yilmaz, M. Bertan, additional, Redwine, David, additional, Putman, Michael, additional, Gurates, Bilgin, additional, Attar, Rukset, additional, Yaegashi, Nobuo, additional, Hales, Dale B., additional, and Bulun, Serdar E., additional

Published
2009
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22. Vulvar Basal Cell Carcinoma with Cliloral Involvement.

Author

Celik, Husnu, Gurates, Bilgin, Yavuz, Adem, Dogan, Zeynep, Cobanoglu, Bengu, and Saral, Yunus

Subjects
*LETTERS to the editor, *BASAL cell carcinoma
Abstract

A letter to the editor is presented which discusses a medical case study of a 72-year-old woman who has a basal cell carcinoma and its treatment.

Published
2009
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23. Prostaglandin E2 Via Steroidogenic Factor-1 Coordinately Regulates Transcription of Steroidogenic Genes Necessary for Estrogen Synthesis in Endometriosis

Author

Hideki Tokunaga, Gonca Imir, Erkut Attar, David Redwine, Dale B. Hales, Rukset Attar, Bilgin Gurates, Nobuo Yaegashi, M. Bertan Yilmaz, Serdar E. Bulun, Michael Putman, [Attar, Erkut -- Tokunaga, Hideki -- Imir, Gonca -- Yilmaz, M. Bertan -- Bulun, Serdar E.] Northwestern Univ, Feinberg Sch Med, Dept Obstet & Gynecol, Div Reprod Biol Res, Chicago, IL 60611 USA -- [Attar, Erkut] Istanbul Univ, Capa Sch Med, Dept Obstet & Gynecol, Istanbul, Turkey -- [Tokunaga, Hideki -- Yaegashi, Nobuo] Tohoku Univ, Dept Obstet & Gynecol, Sendai, Miyagi 9808575, Japan -- [Redwine, David] Cumhuriyet Univ, Sch Med, Dept Obstet & Gynecol, Sivas, Turkey -- [Redwine, David] St Charles Hosp, Dept Obstet & Gynecol, Bend, OR 97701 USA -- [Putman, Michael] Baylor Univ Hosp, Dept Obstet & Gynecol, Dallas, TX 75246 USA -- [Gurates, Bilgin] Firat Univ, Dept Obstet & Gynecol, Sch Med, TR-23169 Elazig, Turkey -- [Attar, Rukset] Yeditepe Univ Hosp, Dept Obstet & Gynecol, Istanbul, Turkey -- [Hales, Dale B.] Univ Illinois, Dept Mol Physiol & Biophys, Chicago, IL 60612 USA, and yilmaz, bertan -- 0000-0001-5558-3299

Subjects
Steroidogenic factor 1, Transcription, Genetic, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Steroidogenic Factor 1, Endometrium, Biochemistry, chemistry.chemical_compound, Endocrinology, Obstetrics and gynaecology, Cytochrome P-450 Enzyme System, Ovarian Diseases, Aromatase, Promoter Regions, Genetic, Cells, Cultured, Progesterone, Regulation of gene expression, Estradiol, biology, Steroidogenic acute regulatory protein, General Medicine, Middle Aged, University hospital, medicine.anatomical_structure, Female, Original Article, Adult, endocrine system, medicine.medical_specialty, medicine.drug_class, Endometriosis, Estrone, Dinoprostone, Gene Expression Regulation, Enzymologic, Young Adult, Translational Highlights from Jcem, Internal medicine, medicine, Humans, Molecular Biology, Estrogen synthesis, business.industry, urogenital system, Biochemistry (medical), Promoter, Phosphoproteins, chemistry, Estrogen, Family medicine, Molecular physiology, biology.protein, business
Abstract

WOS: 000263072700045, PubMed ID: 19001523, Context: Products of at least five specific steroidogenic genes, including steroidogenic acute regulatory protein (StAR), which facilitates the entry of cytosolic cholesterol into the mitochondrion, side chain cleavage P450 enzyme, 3 beta-hydroxysteroid-dehydrogenase-2, 17-hydroxylase/17-20-lyase, and aromatase, which catalyzes the final step, are necessary for the conversion of cholesterol to estrogen. Expression and biological activity of StAR and aromatase were previously demonstrated in endometriosis but not in normal endometrium. Prostaglandin E-2 (PGE(2)) induces aromatase expression via the transcriptional factor steroidogenic factor-1 (SF1) in endometriosis, which is opposed by chicken-ovalbumin upstream- transcription factor (COUP-TF) and Wilms' tumor-1 (WT1) in endometrium. Objective: The aim of the study was to demonstrate a complete steroidogenic pathway leading to estrogen biosynthesis in endometriotic cells and the transcriptional mechanisms that regulate basal and PGE(2)-stimulated estrogen production in endometriotic cells and endometrium. Results: Compared with normal endometrial tissues, mRNA levels of StAR, side chain cleavage P450, 3 beta-hydroxysteroid- dehydrogenase-2, 17-hydroxylase/17-20-lyase, aromatase, and SF1 were significantly higher in endometriotic tissues. PGE(2) induced the expression of all steroidogenic genes; production of progesterone, estrone, and estradiol; and StAR promoter activity in endometriotic cells. Overexpression of SF1 induced, whereas COUP-TFII or WT1 suppressed, StAR promoter activity. PGE(2) induced coordinate binding of SF1 to StAR and aromatase promoters but decreased COUP-TFII binding in endometriotic cells. COUP-TFII or WT1 binding to both promoters was significantly higher in endometrial compared with endometriotic cells. Conclusion: Endometriotic cells contain the full complement of steroidogenic genes for de novo synthesis of estradiol from cholesterol, which is stimulated by PGE(2) via enhanced binding of SF1 to promoters of StAR and aromatase genes in a synchronous fashion. (J Clin Endocrinol Metab 94: 623-631, 2009), National Institutes of Health [HD38691, HD40093]; Friends of Prentice, This work was supported by grants from the National Institutes of Health (HD38691 and HD40093) and Friends of Prentice.

Published
2009

24. A case of vogt-koyanagi-harada disease associated with polycystic ovary syndrome.

Author

Kaya MK, Turgut B, Demir T, Celiker U, and Gurates B

Abstract

Unlabelled: We report a female patient diagnosed as Vogt-Koyanagi-Harada (VKH) and polycystic ovary syndrome (PCOS). She has diagnosed as VKH with diminished vision, bilateral serous retinal detachment, the signs of fundus fluorescein angiography and the findings of optical coherence tomography. The patient was referred to the gynecology clinic for her complaints as weight gain, hirsutismus and amenorrhea. She has also been diagnosed with PCOS. With oral steroid treatment, visual acuity has improved and the detachments have resolved within a month. VKH disease may be associated with polycystic ovary syndrome. The two conditions may have a common autoimmune pathogenesis., Keywords: Autoimmune pathogenesis; Polycystic ovary syndrome; Vogt-Koyanagi-Harada.

Published
2011
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25. Combating endometriosis by blocking proteasome and nuclear factor-kappaB pathways.

Author

Celik O, Hascalik S, Elter K, Tagluk ME, Gurates B, and Aydin NE

Subjects
Animals, Antigens, CD34 biosynthesis, Azo Compounds pharmacology, Boronic Acids therapeutic use, Bortezomib, Case-Control Studies, Eosine Yellowish-(YS) pharmacology, Female, Ki-67 Antigen biosynthesis, Methyl Green pharmacology, Platelet Endothelial Cell Adhesion Molecule-1 biosynthesis, Proliferating Cell Nuclear Antigen biosynthesis, Pyrazines therapeutic use, Pyrrolidines therapeutic use, Rats, Thiocarbamates therapeutic use, Endometriosis drug therapy, NF-kappa B antagonists & inhibitors, Protease Inhibitors therapeutic use, Proteasome Inhibitors
Abstract

Background: The objective of this study is to investigate the effect of pyrrolidine dithiocarbamate [PDTC; a nuclear factor-kappaB (NF-kappaB) inhibitor] and bortezomib (Velcade; a proteasome inhibitor) on the development of experimental endometriotic implants in rats., Methods: Endometriosis was surgically induced in 30 rats using the method of Vernon and Wilson. Three weeks later the viability and volume of the implants were recorded and classified. Afterwards, rats were put into three groups with equal numbers. The groups were labelled as the control, the PDTC and the bortezomib groups. Seven days after treatment, a third laparotomy was done and the volume of implants was measured again. The animals were then sacrificed, and the implants were stained with Ki67, proliferating cell nuclear antigen (PCNA), CD34, CD31 and Masson's trichrome histochemical staining., Results: In 80% of the implanted rats, vesicles at the suture region were observed, and the rats graded according to average vesicle diameter (D) as: Grade 1 (no vesicle, 20% of rats), Grade 2 (D < 2 mm, 33.3% of rats), Grade 3 (2 mm 4.5 mm, 26.7% of rats) and Grade 4 (D > 4.5 mm, 20% of rats). After treatment with PDTC or bortezomib, these percentages were decreased for Grades 3 and 4, and increased in Grade 1. The post-treatment implant volumes were decreased in the PDTC and bortezomib groups (P < 0.002 and P < 0.001), and slightly increased in the control group (P = 0.279). In the PDTC and bortezomib groups, CD34, CD31, PCNA and Ki67 expression levels were similar but were significantly reduced compared with the control group., Conclusions: PDTC and bortezomib may represent a novel therapeutic strategy for treatment of endometriosis.

Published
2008
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