ArticleCell reports2018
Estrogen Deficiency Promotes Hepatic Steatosis via a Glucocorticoid Receptor-Dependent Mechanism in Mice.
Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 92 citations in OpenAlex.
- Sex differences in hepatitis A virus infection in mice.PLoS pathogens · 2026Article
- Targeting Mitochondria in MASLD: Comparative Evaluation of MitoQ and SS-31 (Elamipretide) in Aged Female Mice under Nutritional Stress.Physiological research · 2026Article
- Barley sprouts as a modulator of the gut microbiota, influencing glucose and lipid metabolism in ovariectomized female rats fed a high-fat diet.Nutrition research and practice · 2026Article
- Follicle-Stimulating Hormone in Peripheral Metabolism: Novel Insights into Growth Regulation and Potential Applications in Boar Production.Animals : an open access journal from MDPI · 2026Review
- Mechanical Insights into the Distinct Effects of Ovariectomy Versus Adrenalectomy on Age-Related Thymic Atrophy in Female Mice.International journal of molecular sciences · 2026Article
- Serum free and bioavailable rather than total testosterone is associated with the progression of non-alcoholic fatty liver disease in postmenopausal women: a prospective study.Frontiers in endocrinology · 2026Article
- Development and progression of hepatic steatosis during long-term glucocorticoid therapy in autoimmune hepatitis: multimodal evidence from biopsy, CAP, and ultrasound.Frontiers in medicine · 2026Article
- Risk factors for acute fatty liver of pregnancy complicated by acute liver failure: a retrospective study of 133 cases.BMC pregnancy and childbirth · 2025Article
- Recent advances in anterior pituitary hormones and metabolic-associated fatty liver disease.Frontiers in endocrinology · 2025Review
- HFD feeding for seven months abolishes STING disruption-driven but not female sex-based protection against hepatic steatosis and inflammation in mice.The Journal of nutritional biochemistry · 2025Article
- The role of hepatic sinusoidal microenvironment in NASH: pathogenesis, animal models, and therapeutic prospects.Frontiers in pharmacology · 2025Review
- Prospective associations of leucocyte subtypes and obesity with the risk of developing cutaneous malignant melanoma in the UK Biobank cohort.BMC cancer · 2024Article
- Effects of follicle-stimulating hormone on energy balance and tissue metabolic health after loss of ovarian function.American journal of physiology. Endocrinology and metabolism · 2024Article
- Impact of ovary-intact menopause in a mouse model of heart failure with preserved ejection fraction.American journal of physiology. Heart and circulatory physiology · 2024Article
- Links between the genetic determinants of morning plasma cortisol and body shape: a two-sample Mendelian randomisation study.Scientific reports · 2024Article
- Menopausal characteristics and hormone replacement therapy in relation to long-term risk of cholecystectomy in women.Frontiers in medicine · 2024Article
- Glucocorticoids, their uses, sexual dimorphisms, and diseases: new concepts, mechanisms, and discoveries.Physiological reviews · 2024Review
- Hepatic-Specific FGF21 Knockout Abrogates Ovariectomy-Induced Obesity by Reversing Corticosterone Production.International journal of molecular sciences · 2023Article
- Gut Microbiota and Acylcarnitine Metabolites Connect the Beneficial Association between Estrogen and Lipid Metabolism Disorders in Ovariectomized Mice.Microbiology spectrum · 2023Article
- α1 Adrenoreceptor antagonism mitigates extracellular mitochondrial DNA accumulation in lung fibrosis models and in patients with idiopathic pulmonary fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2023Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Glucocorticoids (GCs) are master regulators of systemic metabolism. Intriguingly, Cushing's syndrome, a disorder of excessive GCs, phenocopies several menopause-induced metabolic pathologies. Here, we show that the glucocorticoid receptor (GR) drives steatosis in hypogonadal female mice because hepatocyte-specific GR knockout mice are refractory to developing ovariectomy-induced steatosis. Intriguingly, transcriptional profiling revealed that ovariectomy elicits hepatic GC hypersensitivity globally. Hypogonadism-induced GC hypersensitivity results from a loss of systemic but not hepatic estrogen (E2) signaling, given that hepatocyte-specific E2 receptor deletion does not confer GC hypersensitivity. Mechanistically, enhanced chromatin recruitment and ligand-dependent hyperphosphorylation of GR underlie ovariectomy-induced glucocorticoid hypersensitivity. The dysregulated glucocorticoid-mediated signaling present in hypogonadal females is a product of increased follicle-stimulating hormone (FSH) production because FSH treatment in ovary-intact mice recapitulates glucocorticoid hypersensitivity similar to hypogonadal female mice. Our findings uncover a regulatory axis between estradiol, FSH, and hepatic glucocorticoid receptor signaling that, when disrupted, as in menopause, promotes hepatic steatosis.
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Registered trials
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.