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Article

Estradiol Regulates mRNA Levels of Estrogen Receptor Beta 4 and Beta 5 Isoforms and Modulates Human Granulosa Cell Apoptosis

1
BFA, UMR 8251, CNRS, ERL U1133, Inserm, Université de Paris, F-75013 Paris, France
2
Service de Médecine de la Reproduction et Préservation de la Fertilité, Hôpital Antoine Béclère, 92140 Clamart, France
3
Lixoft, 8 rue de la Renaissance, Bâtiment D, 92160 Antony, France
*
Author to whom correspondence should be addressed.
Academic Editor: Gabriella Castoria
Int. J. Mol. Sci. 2021, 22(9), 5046; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22095046
Received: 13 April 2021 / Revised: 27 April 2021 / Accepted: 6 May 2021 / Published: 10 May 2021
(This article belongs to the Special Issue Hormones and Receptors in Sexual Reproduction)
Estrogen receptor beta (ERβ) plays a critical role in granulosa cell (GC) functions. The existence of four human ERβ splice isoforms in the ovary suggests their differential implication in 17β-estradiol (E2) actions on GC apoptosis causing follicular atresia. In this study, we investigated whether E2 can regulate ERβ isoforms expression to fine tune its apoptotic activities in human GC. For this purpose, we measured by RT-qPCR the expression of ERβ isoforms in primary culture of human granulosa cells (hGCs) collected from patients undergoing in vitro fertilization, before and after E2 exposure. Besides, we assessed the potential role of ERβ isoforms on cell growth and apoptosis after their overexpression in a human GC line (HGrC1 cells). We confirmed that ERβ1, ERβ2, ERβ4, and ERβ5 isoform mRNAs were predominant over that of ERα in hGCs, and found that E2 selectively regulates mRNA levels of ERβ4 and ERβ5 isoforms in these cells. In addition, we demonstrated that overexpression of ERβ1 and ERβ4 in HGrC1 cells increased cell apoptosis by 225% while ERβ5 or ERβ2 had no effect. Altogether, our study revealed that E2 may influence GC fate by specifically regulating the relative abundance of ERβ isoforms mRNA to modulate the balance between pro-apoptotic and non-apoptotic ERβ isoforms. View Full-Text
Keywords: estrogen receptor; isoforms; human granulosa cells; apoptosis estrogen receptor; isoforms; human granulosa cells; apoptosis
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MDPI and ACS Style

Pierre, A.; Mayeur, A.; Marie, C.; Cluzet, V.; Chauvin, J.; Frydman, N.; Grynberg, M.; Cohen-Tannoudji, J.; Guigon, C.J.; Chauvin, S. Estradiol Regulates mRNA Levels of Estrogen Receptor Beta 4 and Beta 5 Isoforms and Modulates Human Granulosa Cell Apoptosis. Int. J. Mol. Sci. 2021, 22, 5046. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22095046

AMA Style

Pierre A, Mayeur A, Marie C, Cluzet V, Chauvin J, Frydman N, Grynberg M, Cohen-Tannoudji J, Guigon CJ, Chauvin S. Estradiol Regulates mRNA Levels of Estrogen Receptor Beta 4 and Beta 5 Isoforms and Modulates Human Granulosa Cell Apoptosis. International Journal of Molecular Sciences. 2021; 22(9):5046. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22095046

Chicago/Turabian Style

Pierre, Alice, Anne Mayeur, Clémentine Marie, Victoria Cluzet, Jonathan Chauvin, Nelly Frydman, Michael Grynberg, Joelle Cohen-Tannoudji, Céline J. Guigon, and Stéphanie Chauvin. 2021. "Estradiol Regulates mRNA Levels of Estrogen Receptor Beta 4 and Beta 5 Isoforms and Modulates Human Granulosa Cell Apoptosis" International Journal of Molecular Sciences 22, no. 9: 5046. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22095046

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