ArticleObesity (Silver Spring, Md.)2008
Estradiol and the estradiol metabolite, 2-hydroxyestradiol, activate AMP-activated protein kinase in C2C12 myotubes.
Article in Obesity (Silver Spring, Md.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Menstrual cycle hormones and oral contraceptives: a multimethod systems physiology-based review of their impact on key aspects of female physiology.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Pooled it
- Effect of oral contraceptive consumption timing on substrate metabolism, cognition, and exercise performance in females: a randomised controlled trial.European journal of applied physiology · 2025Trial
- Synthetic estrogen and progestin effects on the myogenic program following damage in C2C12 murine myoblasts.Physiological reports · 2026Article
- Metformin use in prediabetes: A review of evidence and a focus on metabolic features among peri-menopausal women.Diabetes, obesity & metabolism · 2025Review
- Dietary resveratrol improves immunity and antioxidant defense in ewes by regulating the rumen microbiome and metabolome across different reproductive stages.Frontiers in immunology · 2024Article
- Understanding the female athlete: molecular mechanisms underpinning menstrual phase differences in exercise metabolism.European journal of applied physiology · 2023Review
- Article
- 17β-Estradiol Treatment Improves Acetylcholine-Induced Relaxation of Mesenteric Arteries in Ovariectomized UC Davis Type 2 Diabetes Mellitus Rats in Prediabetic State.Frontiers in physiology · 2022Article
- Article
- Review
- Multiple Roles in Neuroprotection for the Exercise Derived Myokine Irisin.Frontiers in aging neuroscience · 2021Review
- The Impact of Skeletal Muscle ERα on Mitochondrial Function and Metabolic Health.Endocrinology · 2020Review
- Ginger Extract Increases GLUT-4 Expression Preferentially Through AMPK Than PI3K Signalling Pathways in C2C12 Muscle Cells.Diabetes, metabolic syndrome and obesity : targets and therapy · 2020Article
- Molecular mechanisms of estrogen receptorThe Journal of international medical research · 2019Review
- The impact of ERα action on muscle metabolism and insulin sensitivity - Strong enough for a man, made for a woman.Molecular metabolism · 2018Review
- The clinical impact of estrogen loss on cardiovascular disease in menopausal females.Medical research archives · 2018Article
- Estradiol does not directly regulate adipose lipolysis.Adipocyte · 2017Article
- Estradiol modulates myosin regulatory light chain phosphorylation and contractility in skeletal muscle of female mice.American journal of physiology. Endocrinology and metabolism · 2016Article
- Impaired estrogen receptor action in the pathogenesis of the metabolic syndrome.Molecular and cellular endocrinology · 2015Review
- Skeletal muscle AMP-activated protein kinase γ1(H151R) overexpression enhances whole body energy homeostasis and insulin sensitivity.American journal of physiology. Endocrinology and metabolism · 2015Article
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4 authors.
Funding
Abstract
objectiveSystemic loss of estradiol (E2) during menopause is associated with increased adiposity which can be prevented with E2 replacement. Rodent studies suggest that E2, or lack of, is a key mediator in menopause-related metabolic changes. We have previously demonstrated that E2 treatment produces a rapid, dose-dependent activation of AMP-activated protein kinase (AMPK) in murine skeletal muscle. Activation of AMPK is implicated in the therapeutic benefits of many insulin sensitizing agents including metformin and thiazolidinediones. Here, we expand our observations and provide novel data which demonstrate that in addition to E2, its metabolite 2-hydroxyestradiol (2-HE2), activate AMPK in C2C12 myotubes. METHODS AND PROCEDURES: C2C12 myotubes were used to examine the effects on E2 and the by-products of its metabolism on AMPK activation.
resultsLow concentrations of E2 (10 and 100 nmol/l) were found to increase AMPK phosphorylation by approximately 1.6-fold, while a higher concentration (10 micromol/l) resulted in a approximately 3.0-fold increase. In comparison to E2 treatment alone, incubation of myotubes with E2 and 1-aminobenzotriazole (ABT) (a CYP450 inhibitor that blocks metabolism of E2) caused AMPK activation to be enhanced at low E2 concentrations, but attenuated at higher concentrations. The effects of ABT suggested that one or more E2 metabolites contribute to the maximal activation of AMPK at high E2 concentrations. Indeed, the estrogen metabolite 2-HE2, but not 2-methoxyestradiol (2-ME2), directly activated AMPK in C2C12 myotubes. DISCUSSION: We propose a model where E2, acting through its metabolite 2-HE2 and the estrogen receptors (ERs), activates AMPK in myotubes. Finally, activation is abolished when all E2 is metabolized to 2-ME2.
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