Alice Pierre1,2,3, Joëlle Taieb1,2,3, Frank Giton4, Michaël Grynberg1,2,3, Salma Touleimat1,2,3, Hady El Hachem1,2,3, Renato Fanchin1,2,3, Danielle Monniaux5,6,7,8, Joëlle Cohen-Tannoudji1,2,3, Nathalie di Clemente1,2,3, Chrystèle Racine1,2,3. 1. Université Paris Diderot, Sorbonne Paris Cité, F-75013 Paris, France. 2. Institut National de la Santé et de la Recherche Médicale Unité 1133, Physiologie de l'Axe Gonadotrope, F-75013 Paris, France. 3. Centre National de la Recherche Scientifique, UMR8251, Biologie Fonctionnelle et Adaptative, F-75013 Paris, France. 4. Assistance Publique-Hôpitaux de Paris, Centre d'Investigations Biologiques GHU, INSERM IMRB U955, Centre de Recherche Chirurgicales, Hopital Henri Mondor, Créteil F-94010, France. 5. Institut National de la Recherche Agronomique, UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France. 6. Centre National de la Recherche Scientifique, UMR7247, F-37380 Nouzilly, France. 7. Université François Rabelais de Tours, F-37041 Tours, France. 8. Institut Français du Cheval et de l'Equitation, F-37380 Nouzilly, France.
Abstract
Context: Anti-Müllerian hormone (AMH) and AMH type II receptor (AMHR2) are overexpressed in granulosa cells (GCs) from women with polycystic ovary syndrome (PCOS), the most common cause of female infertility. Objective: The aim of the study was to compare the regulation of the AMH/AMHR2 system by 5α-dihydrotestosterone (5α-DHT) and estradiol (E2) in GCs from control subjects and women with PCOS. Design, Setting, Patients: Experiments were performed on follicular fluids (FF) and GCs from women undergoing in vitro fertilization. Main Outcome Measures: FF steroid levels were measured by mass spectrometry, and messenger RNA (mRNA) accumulation was quantified by reverse transcription real-time polymerase chain reaction. Results: Total testosterone (T), free T, and 5α-DHT FF levels were significantly higher (P < 0.001) in women with PCOS than in controls. However, E2 and sex hormone-binding globulin concentrations were comparable between the two groups. In GCs from control women, the AMH and AMHR2 expression were not affected by 5α-DHT treatment, whereas AMH mRNA levels were upregulated by 5α-DHT in GCs from patients with PCOS (2.3-fold, P < 0.01) overexpressing the androgen receptor (1.4-fold, P < 0.05). E2 downregulated the AMH and AMHR2 expression in GCs from control women (1.4-fold, P < 0.001 and 1.8-fold, P < 0.01, respectively) but had no effect on these genes in GCs from women with PCOS. This differential effect of E2 was associated with a higher estrogen receptor 1 expression in GCs from women with PCOS (1.9-fold, P < 0.05). Conclusions: In GCs from women with PCOS, the regulation of AMH and AMHR2 expression is altered in a way that promotes the overexpression of the AMH/AMHR2 system, and could contribute to the follicular arrest observed in these patients.
Context: Anti-Müllerian hormone (AMH) and AMH type II receptor (AMHR2) are overexpressed in granulosa cells (GCs) from women with polycystic ovary syndrome (PCOS), the most common cause of female infertility. Objective: The aim of the study was to compare the regulation of the AMH/AMHR2 system by 5α-dihydrotestosterone (5α-DHT) and estradiol (E2) in GCs from control subjects and women with PCOS. Design, Setting, Patients: Experiments were performed on follicular fluids (FF) and GCs from women undergoing in vitro fertilization. Main Outcome Measures: FF steroid levels were measured by mass spectrometry, and messenger RNA (mRNA) accumulation was quantified by reverse transcription real-time polymerase chain reaction. Results: Total testosterone (T), free T, and 5α-DHT FF levels were significantly higher (P < 0.001) in women with PCOS than in controls. However, E2 and sex hormone-binding globulin concentrations were comparable between the two groups. In GCs from control women, the AMH and AMHR2 expression were not affected by 5α-DHT treatment, whereas AMH mRNA levels were upregulated by 5α-DHT in GCs from patients with PCOS (2.3-fold, P < 0.01) overexpressing the androgen receptor (1.4-fold, P < 0.05). E2 downregulated the AMH and AMHR2 expression in GCs from control women (1.4-fold, P < 0.001 and 1.8-fold, P < 0.01, respectively) but had no effect on these genes in GCs from women with PCOS. This differential effect of E2 was associated with a higher estrogen receptor 1 expression in GCs from women with PCOS (1.9-fold, P < 0.05). Conclusions: In GCs from women with PCOS, the regulation of AMH and AMHR2 expression is altered in a way that promotes the overexpression of the AMH/AMHR2 system, and could contribute to the follicular arrest observed in these patients.
Authors: Loes M E Moolhuijsen; Yvonne V Louwers; Anke McLuskey; Linda Broer; Andre G Uitterlinden; Renée M G Verdiesen; Ryan K Sisk; Andrea Dunaif; Joop S E Laven; Jenny A Visser Journal: Hum Reprod Date: 2022-06-30 Impact factor: 6.353
Authors: Ewa Rudnicka; Michał Kunicki; Anna Calik-Ksepka; Katarzyna Suchta; Anna Duszewska; Katarzyna Smolarczyk; Roman Smolarczyk Journal: Int J Mol Sci Date: 2021-11-19 Impact factor: 5.923