ArticleFrontiers in endocrinology2019
17β-Estradiol Inhibits PCSK9-Mediated LDLR Degradation Through GPER/PLC Activation in HepG2 Cells.
Article in Frontiers in endocrinology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 3 of them syntheses 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.
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Who cites it
33 citing papers in PubMed, 3 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- When bad turns good: a systematic review on cholesterol and LDL in longitudinal patient cohorts with Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Pooled it
- Exploring associations between estrogen and gene candidates identified by coronary artery disease genome-wide association studies.Frontiers in cardiovascular medicine · 2025Pooled it
- A Systematic Review on Attenuation of PCSK9 in Relation to Atherogenesis Biomarkers Associated with Natural Products or Plant Bioactive Compounds in In Vitro Studies: A Critique on the Quality and Imprecision of Studies.International journal of environmental research and public health · 2022Pooled it
- PCSK9 Inhibitor Use and the Risk of Age-Related Macular Degeneration in Patients with Atherosclerotic Cardiovascular Disease.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Estrogen deprivation induces hepatic inflammation, Indoleamine-2,3-dioxygenase 1, tryptophan catabolism, and plasma cholesterol.Scientific reports · 2026Article
- Exploring sex bias in cardiometabolic diseases.Lipids in health and disease · 2026Review
- Review
- Gender and region disparities in plasma PCSK9 levels: a systematic review and meta-analysis.BMJ public health · 2026Article
- The Impact of Estrogen Deficiency on Liver Metabolism: Implications for Hormone Replacement Therapy.Endocrine reviews · 2025Review
- Independent validation of lung adenocarcinoma prognostic risk scores incorporating cholesterol and estrogen metabolism related transcriptional biomarkers.Scientific reports · 2025Article
- Metabolic and Endocrine Alterations in Underweight and Normal-Weight Women with Functional Hypothalamic Amenorrhea.Journal of clinical medicine · 2025Article
- Obesity alters VLDL profile and remnant cholesterol differently in metabolically healthy men and women: a ¹H-NMR study.Lipids in health and disease · 2025Article
- Decreased protein activator of interferon induced protein kinase (PRKRA) involved in menopause-related cholesterol metabolic disorders by regulating cholesterol biosynthesis.Lipids in health and disease · 2025Article
- Unraveling Estrogen and PCSK9's Roles in Lipid Metabolism Disorders among Ovariectomized Mice.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Lipid Lowering Therapy Utilization and Lipid Goal Attainment in Women.Current atherosclerosis reports · 2025Review
- Sex hormones differently regulate lipid metabolism genes in primary human hepatocytes.BMC endocrine disorders · 2024Article
- Lipoprotein Metabolism, Dyslipidemia, and Lipid-Lowering Therapy in Women: A Comprehensive Review.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Research on Hepatocyte Regulation of PCSK9-LDLR and Its Related Drug Targets.Chinese journal of integrative medicine · 2024Review
- Effects of Serum Estradiol on Proprotein Convertase Subtilisin/Kexin Type 9 Levels and Lipid Profiles in Women Undergoing In Vitro Fertilization.Journal of cardiovascular development and disease · 2024Article
- Selective Activation of G Protein-coupled Estrogen Receptor 1 Attenuates Atherosclerosis.Current medicinal chemistry · 2024Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plasma levels of PCSK9 are significantly higher in postmenopausal women. Pharmacologically increased estrogen levels have been shown to lower PCSK9 and LDL-C levels in animals and humans. The action of estrogen suggests that it has the ability to prevent PCSK9-mediated LDLR degradation in liver cells. However, little is known about how estrogen alters PCSK9-mediated LDLR degradation. Here, we report that 17β-estradiol (βE2) reduces PCSK9-mediated LDLR degradation by a mechanism that involves activation of the G protein-coupled estrogen receptor (GPER). In cultured HepG2 cells, βE2 prevented the internalization of PCSK9, which subsequently lead to PCSK9-mediated LDLR degradation. The altered LDLR levels also resulted in an increase in LDL uptake that was not observed in the absence of PCSK9. In addition, we showed that clathrin was rapidly increased in the presence of PCSK9, and this increase was blocked by βE2 incubation, suggesting rapid recruitment of clathrin in HepG2 cells. PLCγ activation and intracellular Ca
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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.