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Published on: February 21, 2014
Estradiol Regulates mRNA Levels of Estrogen Receptor Beta 4 and Beta 5 Isoforms and Modulates Human Granulosa Cell
Alice Pierre1, Anne Mayeur2, Clémentine Marie1
1BFA, UMR 8251, CNRS, ERL U1133, Inserm, Université de Paris, F-75013 Paris, France.
Abstract:
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.
Insights
17β-estradiol (E2) regulates specific estrogen receptor beta (ERβ) isoforms in human granulosa cells. This selective regulation fine-tunes E2
Area of Science:
- Reproductive Endocrinology
- Molecular Biology
- Cell Biology
Background:
- Estrogen receptor beta (ERβ) is crucial for granulosa cell (GC) function.
- Four human ERβ splice isoforms exist in the ovary, potentially mediating differential 17β-estradiol (E2) effects on GC apoptosis and follicular atresia.
Purpose of the Study:
- To investigate if E2 regulates ERβ isoform expression in human GCs.
- To determine the role of ERβ isoforms in modulating GC apoptosis and proliferation.
Main Methods:
- Primary human granulosa cells (hGCs) from IVF patients were cultured.
- ERβ isoform mRNA levels were quantified using RT-qPCR before and after E2 exposure.
- ERβ isoform function was assessed via overexpression in the HGrC1 cell line.
Main Results:
- ERβ1, ERβ2, ERβ4, and ERβ5 mRNA were predominant in hGCs.
- E2 selectively modulated ERβ4 and ERβ5 mRNA levels.
- Overexpression of ERβ1 and ERβ4 significantly increased apoptosis (225%), while ERβ2 and ERβ5 had no effect.
Conclusions:
- E2 influences GC fate by regulating the relative abundance of ERβ isoforms.
- This regulation modulates the balance between pro-apoptotic and non-apoptotic ERβ isoforms, impacting follicular atresia.
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