New-D-homoandrost-4,6-diene derivatives as potent progesterone receptor antagonist |
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| Authors: | Marisa Cabeza Mario García-Lorenzana Montserrat Garcés Ivonne Heuze Nayeli Teran Eugene Bratoeff |
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| Affiliation: | 1. Department of Biological Systems and Animal Production Metropolitan University-Xochimilco, Mexico D. F., Mexico;2. Department of Biology of Reproduction, Metropolitan University-Iztapalapa, Mexico D. F., Mexico;3. Department of Pharmacy, Faculty of Chemistry, National University of Mexico City, Mexico D. F., Mexico;1. Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan;2. Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan;1. State Key Laboratory of Pollution Control and Resources Reuse, School of the Environment, Nanjing University, Nanjing 210046, People’s Republic of China;2. Department of Veterinary Biomedical Sciences and Toxicology Centre, University of Saskatchewan, Saskatoon, SK, Canada;3. Department of Zoology and Center for Integrative Toxicology, Michigan State University, East Lansing, MI, USA;4. School of Biological Sciences, University of Hong Kong, Hong Kong, SAR, People’s Republic of China;5. Biology and Chemistry, and State key Laboratory for Marine Pollution, City University of Hong Kong, Hong Kong, SAR, People’s Republic of China;1. Department of Obstetrics-Gynecology, The Oncology Institute Prof. Dr. Ion Chiricuta, Cluj-Napoca, Romania;2. University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania;3. Department of Pathology, Clinical Hospital Dr. Gavril Curteanu, Oradea, Romania;4. Pathology Department at University of Oradea, Faculty of Medicine and Pharmacy, Oradea, Romania;5. Department of Mechanical Systems Engineering, The Technical University, Cluj-Napoca, Romania;6. Department of Obstetrics and Gynecology, University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania;7. Obstetrics and Gynecology Department, County Hospital of Cluj, Romania;1. Institute of Laboratory Medicine, University of Pécs, Pécs H-7624, Hungary;2. Department of Biochemistry and Medical Chemistry, University of Pécs, Pécs H-7624, Hungary;3. Department of Pharmacognosy, Faculty of Pharmacy and Biochemistry, University of Zagreb, HR-10000 Zagreb, Croatia;4. Department of Medical Biochemistry and Haematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, HR-10000 Zagreb, Croatia;1. Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Malaysia;2. Faculty of Dentistry, Universiti Sains Islam Malaysia, Jalan Pandan Indah, 55100 Kuala Lumpur, Malaysia;3. Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Malaysia;4. Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Malaysia;1. Tel-Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel;2. Department of Obstetrics and Gynecology, Brigham and Women’s Hospital, Boston, MA 02115, USA;3. Vascular Biology Program, Department of Surgery, Children’s Hospital Boston, both at Harvard Medical School, Boston, MA 02115, USA;4. Laboratory for Reproductive Immunology, Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Faculty of Medicine, Technion – Israel Institute of Technology, P.O. Box 169, Hadera 38100, Israel;5. IVF Unit, Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Faculty of Medicine, Technion – Israel Institute of Technology, P.O. Box 169, Hadera 38100, Israel |
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| Abstract: | The aim of this study was to synthesize three different D-homoandrostadiene derivatives (2–4) and study their biological activity. We carried out in vivo and in vitro experiments using female cycling mice, which were synchronized for estrus with luteinizing hormone-releasing hormone (LHRH) and injected with the steroidal compounds. It was also determined the binding of these compounds to the progesterone receptors (PR). Since these steroids have a new D-homoandrostandienone skeleton in their molecular structure, it was of interest also to study their binding to the androgen receptors (AR).After LHRH treatment, the mice of the control group showed the presence of 14 ± 4 corpus lutea in the ovary whereas the animals treated with steroids 2–4, with RBAs of 100%, exhibited 11 ± 7, 12 ± 2, and 10 ± 4 respectively. As a result of this study, it is evident that these steroids did not inhibit the ovulation in these animals.The uterus of the control group, showed the typical progestational activity with an enlarged endometrial thickness with a secretory activity. However, the endometrium of the mice treated with steroids 2–4 did not show an enlargement of the endometrium and no secretory activity could be detected. This fact indicates that compounds 2–4 had antagonistic activity in this tissue.The overall data show that steroids 2–4 are antagonists of the PR. However, they do not bind to the AR. These results also demonstrate that 2–4 have an antiprogestational activity in vivo, but do not decrease the number of corpus lutea in the ovary of mice treated with LHRH. |
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