ArticleExperimental & molecular medicine2019
Estrogen negatively regulates the renal epithelial sodium channel (ENaC) by promoting Derlin-1 expression and AMPK activation.
Article in Experimental & molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 21 citations in OpenAlex.
- Sex-Specific Lipid, Apolipoprotein B, and Lipoprotein(a) Responses to Berberine Based on 2 Randomized Placebo-Controlled Trials.JACC. Asia · 2026Article
- Ovarian hormones moderate systolic hypertension in femaleAmerican journal of physiology. Renal physiology · 2026Article
- Sodium Retention and Distribution in Growing and Adult Rodents Fed High and Low Salt Diets.Nutrients · 2026Article
- The double-edged sword effect of estrogen in kidney disease and its precision modulation.Frontiers in endocrinology · 2026Review
- Ovarian Hormones Moderate Systolic Hypertension in FemalebioRxiv : the preprint server for biology · 2025Article
- Renal G protein-coupled estrogen receptor 1 regulates the epithelial sodium channel promoting natriuresis to a greater extent in females.American journal of physiology. Renal physiology · 2025Article
- Mineralocorticoid and estrogen receptors as sex-dependent modulators of vascular health in aging and obesity.The Journal of pharmacology and experimental therapeutics · 2025Review
- Aging and sex differences in salt sensitivity of blood pressure.Clinical science (London, England : 1979) · 2025Review
- Review
- Effects of sea salt intake on metabolites, steroid hormones, and gut microbiota in rats.PloS one · 2022Article
- Hypertension and human immunodeficiency virus: A paradigm for epithelial sodium channels?Frontiers in cardiovascular medicine · 2022Review
- Article
- Plasma creatine and incident type 2 diabetes in a general population-based cohort: The PREVEND study.Clinical endocrinology · 2021Article
- Knockout of the circadian clock protein PER1 results in sex-dependent alterations of ET-1 production in mice in response to a high-salt diet plus mineralocorticoid treatment.Canadian journal of physiology and pharmacology · 2020Article
- Possible protective role of 17β-estradiol against COVID-19.Journal of allergy and infectious diseases · 2020Article
- Correlation Between Free Thyroxine Levels and Mortality in Hypertensive Patients.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisArticle
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9 authors at 1 institution in 1 country.
Funding
Abstract
The main functions of the epithelial sodium channel (ENaC) in the kidney distal nephron are mediation of sodium and water balance and stabilization of blood pressure. Estrogen has important effects on sodium and water balance and on premenopausal blood pressure, but its role in the regulation of ENaC function is not fully understood. Female Sprague-Dawley rats were treated with 17β-estradiol for 6 weeks following bilateral ovariectomy. Plasma estrogen, aldosterone, creatinine, and electrolytes were analyzed, and α-ENaC and derlin-1 protein expression in the kidney was determined by immunohistochemistry and western blotting. The expression levels of α-ENaC, derlin-1, AMPK, and related molecules were also examined by western blotting and real-time PCR in cultured mouse renal collecting duct (mpkCCDc14) epithelial cells following estrogen treatment. Immunofluorescence and coimmunoprecipitation were performed to detect α-ENaC binding with derlin-1 and α-ENaC ubiquitination. The results demonstrated that the loss of estrogen elevated systolic blood pressure in ovariectomized (OVX) rats. OVX rat kidneys showed increased α-ENaC expression but decreased derlin-1 expression. In contrast, estrogen treatment decreased α-ENaC expression but increased derlin-1 expression in mpkCCDc14 cells. Moreover, estrogen induced α-ENaC ubiquitination by promoting the interaction of α-ENaC with derlin-1 and evoked phosphorylation of AMPK in mpkCCDc14 cells. Our study indicates that estrogen reduces ENaC expression and blood pressure in OVX rats through derlin-1 upregulation and AMPK activation.
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