GnRH agonist and GnRH antagonist protocols in ovarian stimulation: differential regulation pathway of aromatase expression in human granulosa cells |
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| Authors: | Mohamad Khalaf Hervé Mittre Jérôme Levallet Vincent Hanoux Christine Denoual Michel Herlicoviez Pierre-Jacques Bonnamy Annie Benhaim |
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| Affiliation: | 1. Universite de Caen-Basse Normandie, Laboratoire, EA 2608, F-14032 Caen cedex, France;2. INRA, USC 2006, F-14032 Caen cedex, France;3. CHU de Caen, Laboratoire de Fécondation In Vitro, Service de Gynécologie Obstétrique, F-14033 Caen cedex, France;4. CHU de Caen, Laboratoire de Genetique Moleculaire, F-14033 Caen cedex, France;1. OriginElle Fertility Clinic and Women''s Health Centre, Montreal QC;2. Department of Obstetrics and Gynaecology, McGill University, Montreal QC;3. Peking University First Hospital, Peking University, Beijing, China;1. Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California;2. Celmatix, Inc., New York, New York;3. Reproductive Medical Associates of New York, New York, New York;4. Department of Obstetrics and Gynecology, Mount Sinai Icahn School of Medicine, New York, New York;5. Department of Obstetrics and Gynecology, University of Connecticut School of Medicine, Farmington, Connecticut;6. Center for Advanced Reproductive Sciences, Farmington, Connecticut;7. Reproductive Medical Associates of Michigan, Troy, Michigan;8. Shady Grove Fertility Center, Rockville, Maryland |
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| Abstract: | Gonadotrophin-releasing hormone (GnRH) agonists and antagonists have been widely used to prevent premature LH surge during ovarian stimulation. However, studies have shown a significantly lower serum oestradiol concentration on the day of human chorionic gonadotrophin administration for cycles using GnRH antagonist. This study compared aromatase gene expression in granulosa lutein cells from 50 women randomly assigned to receive either GnRH agonist (group 1, n = 28) or GnRH antagonist (group 2, n = 22). The cellular mechanism involved in the observed effects was also investigated. GnRH antagonist treatment significantly affected serum oestradiol concentration (1894 ± 138 versus 1074 ± 63 pg/ml; P ? 0.001), follicular-fluid oestradiol concentration in large follicles (18,565 ± 2467 versus 10,184 ± 1993 pg/ml; P ? 0.05), aromatase activity (9600 ± 1179 versus 5376 ± 997 fmol/106 cells/h; P ? 0.05) and mRNA aromatase/mRNA glyceraldehyde 3-phosphate dehydrogenase (15 ± 3 versus 6 ± 1; P < 0.05). Protein kinase C (PKC) activity in granulosa lutein cells from the GnRH antagonist group was 2.5-fold higher than in the GnRH agonist group. In-vitro experiments showed that selective down-regulation of PKC was only observed in GnRH-desensitized granulosa lutein cells. This report suggests that, in granulosa lutein cells, the modulation of the FSH-induced protein kinase A pathway by PKC was different in agonist versus antagonist cycles. |
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