ArticleThe Journal of biological chemistry2022
FSH mediates estradiol synthesis in hypoxic granulosa cells by activating glycolytic metabolism through the HIF-1α-AMPK-GLUT1 signaling pathway.
Article in The Journal of biological chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- Growth Hormone Reverses Cisplatin-Induced Ovarian Reserve Depletion in Mice: Transcriptomic Elucidation of Mitochondrial Metabolic Reprogramming and Protein Synthesis Regulation.FASEB bioAdvances · 2026Article
- Integrative Transcriptomic Analysis and Functional Validation Implicate GPT2 in Glycolytic Regulation in Polycystic Ovary Syndrome.Food science & nutrition · 2026Article
- Glucose Transporter 1 in Health and Disease.MedComm · 2026Review
- A transcriptomic map of ligand-receptor interactions within bovine antral follicles predicts intrafollicular factors for improving oocyte quality.Journal of animal science and biotechnology · 2026Article
- Bisphenol F-Associated Repeated Breeding Syndrome in Cows: Epidemiological Evidence and Protective Effects of Phillyrin Against Granulosa Cell Injury.Veterinary sciences · 2026Article
- Metformin drives HIF-1α-mediated dual metabolic reprogramming to enhance γδ T cell therapy in triple-negative breast cancer.Cancer immunology, immunotherapy : CII · 2026Article
- PDK4 is critical for metabolic regulation and progesterone production in bovine granulosa cells†.Biology of reproduction · 2026Article
- Morphometric and hormonal correlations in high- and low-yield baizi geese during off-season production.Poultry science · 2026Article
- Integrated proteomic profiling of serum, follicular fluid and ovarian tissue in dairy cows with inactive ovaries.BMC veterinary research · 2026Article
- Seasonal Change in Glucose Metabolism and Steroidogenesis in the Ovaries of Wild Ground Squirrels (Animals : an open access journal from MDPI · 2026Article
- Correlation between ambulatory blood pressure indices and sex hormone imbalance in hypertensive women with different menopausal durations: a cross-sectional study.European journal of medical research · 2026Observational
- Histone Lactylation Couples FSH-Driven Lactate Metabolism to Mitochondrial Biogenesis by Enhancing HDAC4-Mediated Deacetylation of PGC-1α in Granulosa Cells.Research (Washington, D.C.) · 2026Article
- Hypoxia-induced degradation of FTO promotes apoptosis by unmasking RACK1-mediated activation of MTK1-JNK1/2 pathway.Journal of advanced research · 2025Article
- Lactylation of CREB is required for FSH-induced proliferation and differentiation of ovarian granulosa cells.Nucleic acids research · 2025Article
- Potential of growth factors and steroid hormones from cell cultures to improveOpen veterinary journal · 2025Review
- Regulation of early gonocyte differentiation in zebrafish.Biochemical Society transactions · 2025Article
- Review
- Rapamycin Increases the Development Competence of Yak (Animals : an open access journal from MDPI · 2025Article
- From hormones to neurodegeneration: how FSH drives Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
- Molecular pathways affecting reproductive efficiency in seasonal breeders: prospects and implications for improving fertility in donkeys.Frontiers in veterinary science · 2025Review
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Owing to the avascular environment within ovarian follicles, granulosa cells (GCs) are believed to live in a hypoxic niche. Follicle-stimulating hormone (FSH)-mediated steroidogenesis is crucial for normal growth and maturation of ovarian follicles, but it remains unclear how FSH stimulates estradiol (E2) synthesis under hypoxic conditions. Here, we aimed to explore whether FSH affects the ATP production required for estrogen synthesis from the perspective of glucose metabolism. It was observed that the levels of both E2 and HIF-1α were markedly increased in a dose-dependent manner in mouse ovarian GCs after the injection of FSH in vivo, indicating that hypoxia/HIF-1α may be relevant to FSH-induced E2 synthesis. By treating hypoxic GCs with FSH in vitro, we further revealed that the activation of the AMP-activated protein kinase (AMPK)-GLUT1 pathway, which in turn stimulates ATP generation, may be essential for FSH-mediated E2 production during hypoxia. In contrast, inhibition of AMPK or GLUT1 with siRNAs/antagonist both repressed glycolysis, ATP production, and E2 synthesis despite FSH treatment. Moreover, blocking HIF-1α activity using siRNAs/PX-478 suppressed AMPK activation, GLUT1 expression, and E2 levels in FSH-treated GCs. Finally, the in vitro findings were verified in vivo, which showed markedly increased AMPK activity, GLUT1 expression, glycolytic flux, ATP levels, and E2 concentrations in ovarian GCs following FSH injection. Taken together, these findings uncovered a novel mechanism for FSH-regulating E2 synthesis in hypoxic GCs by activating glycolytic metabolism through the HIF-1α-AMPK-GLUT1 pathway.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.