ArticleThe Journal of clinical endocrinology and metabolism2013
Metformin inhibits follicle-stimulating hormone (FSH) action in human granulosa cells: relevance to polycystic ovary syndrome.
Article in The Journal of clinical endocrinology and metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Metformin and gonadotropins for ovulation induction in patients with polycystic ovary syndrome: a systematic review with meta-analysis of randomized controlled trials.Reproductive biology and endocrinology : RB&E · 2014Pooled it
- Ameliorating effects of bromelain with or without metformin on endocrine-metabolic disturbances in letrozole-induced polycystic ovary syndrome in female rats via targeting SIRT1, insulin resistance, and inflammatory axis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Metformin-Driven Activation of Polymorphic Follicle-Stimulating Hormone Receptors for Polycystic Ovary Syndrome Treatment: A Computational Study.Medical science monitor : international medical journal of experimental and clinical research · 2025Article
- Metformin use in women with polycystic ovary syndrome (PCOS): Opportunities, benefits, and clinical challenges.Diabetes, obesity & metabolism · 2025Review
- Beclin 1-Mediated Autophagy Is Potentiated by an Interaction with the Neuronal Adaptor FE65.Biology · 2025Article
- Metformin in gynecological disorders: pathogenic insights and therapeutic implications.Frontiers in pharmacology · 2025Review
- Insulin-sensitizing agents for infertility treatment in woman with polycystic ovary syndrome: a narrative review of current clinical practice.Hormones (Athens, Greece) · 2024Review
- Induced Pluripotent Stem Cells as a Possible Approach for Exploring the Pathophysiology of Polycystic Ovary Syndrome (PCOS).Stem cell reviews and reports · 2024Review
- Investigating the potential role of swertiamarin on insulin resistant and non-insulin resistant granulosa cells of poly cystic ovarian syndrome patients.Journal of ovarian research · 2023Article
- Follicle-Stimulating Hormone Promotes the Development of Endometrial CancerInternational journal of environmental research and public health · 2022Article
- Follicle stimulating hormone promotes production of renin through its receptor in juxtaglomerular cells of kidney.Diabetology & metabolic syndrome · 2022Article
- Review
- Posttranslational modifications in pathogenesis of PCOS.Frontiers in endocrinology · 2022Review
- Role of FSH and FSH receptor on HUVECs migration.Gene therapy · 2021Article
- Article
- Improvement Effect of Metformin on Female and Male Reproduction in Endocrine Pathologies and Its Mechanisms.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Effects of Metformin on Reproductive, Endocrine, and Metabolic Characteristics of Female Offspring in a Rat Model of Letrozole-Induced Polycystic Ovarian Syndrome With Insulin Resistance.Frontiers in endocrinology · 2021Article
- Exploring the roles of fecundity-related long non-coding RNAs and mRNAs in the adrenal glands of small-tailed Han Sheep.BMC genetics · 2020Article
- Characterization and identification of human immortalized granulosa cells derived from ovarian follicular fluid.Experimental and therapeutic medicine · 2019Article
- Follicle-stimulating hormone enhances hepatic gluconeogenesis by GRK2-mediated AMPK hyperphosphorylation at Ser485 in mice.Diabetologia · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundWomen with anovulatory polycystic ovary syndrome (PCOS) are generally insulin-resistant and as a consequence are often treated with the biguanide metformin. Results with metformin have, however, been variable with some studies demonstrating induction of regular cycles and an increase in ovulation, whereas others do not. Hence more understanding is needed regarding the mechanism of metformin's actions in ovarian granulosa cells especially in light of previous demonstrations of direct actions.
objectiveThe aim of this study was to investigate metformin's interaction with the FSH/cAMP/protein kinase A pathway, which is the primary signaling pathway controlling CYP19A1 (aromatase) expression in the ovary.
methodsThe effect of metformin on FSH and forskolin-stimulated aromatase expression in human granulosa cells was measured by quantitative real-time PCR. Activity was assessed after transfection with a promoter II-luciferase construct, and by an RIA measuring conversion of androgen to estrogens. The effect on FSH receptor (FSHR) mRNA was assessed by quantitative PCR. Levels of phosphorylated cAMP response element binding protein (CREB) and CREB-regulated transcription coactivator 2 (CRTC2) were measured by Western blotting and cAMP by a bioluminescent assay.
resultsMetformin markedly reduced FSH but not forskolin-stimulated aromatase expression and activity. This effect was exerted by inhibition of basal and ligand-induced up-regulation of FSHR expression. Metformin also reduced FSH-induced phosphorylation of CREB and hence CRE activity, which could potentially disrupt the CREB-CREB-binding protein-CRTC2 coactivator complex that binds to CRE in promoter II of the aromatase gene. This is mediated in an AMP-activated protein kinase-independent manner, and does not involve alteration of cAMP levels.
conclusionThese finding have implications for the use of metformin in the treatment of anovulation in women with PCOS.
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Registered trials
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