ArticleJournal of the American Society of Nephrology : JASN2016
Adjusting the 17β-Estradiol-to-Androgen Ratio Ameliorates Diabetic Nephropathy.
Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- Sex-Specific Renal Proteomic Responses to Mycotoxins and Their Mitigation by Bioactive Food Ingredients.Molecular nutrition & food research · 2026Article
- Association between circulating sex hormone levels and diabetic kidney disease in men and postmenopausal women with type 2 diabetes mellitus.World journal of diabetes · 2025Article
- Gender Differences in Adenine Diet-Induced Kidney Toxicity: The Impact of 17β-Estradiol on Renal Inflammation and Fibrosis.International journal of molecular sciences · 2025Article
- Therapeutic potential of common Phytoestrogens found in traditional Chinese medicine in chronic kidney diseases.Frontiers in pharmacology · 2025Review
- Differentiation, reduction, and proliferation of pancreatic β-cells and their regulatory factors.Diabetology international · 2025Review
- Sex difference in human diseases: mechanistic insights and clinical implications.Signal transduction and targeted therapy · 2024Review
- The Role of Gender Differences and Menopause in Obesity-Related Renal Disease, Renal Inflammation and Lipotoxicity.International journal of molecular sciences · 2023Article
- Role of Sex Hormones in Prevalent Kidney Diseases.International journal of molecular sciences · 2023Review
- HNF1A binds and regulates the expression of SLC51B to facilitate the uptake of estrone sulfate in human renal proximal tubule epithelial cells.Cell death & disease · 2023Article
- Identification and validation of immune-related biomarkers and potential regulators and therapeutic targets for diabetic kidney disease.BMC medical genomics · 2023Article
- Differences in long-term effects of standard rodent diets on blood glucose and body weight of offspring.Diabetology international · 2022Article
- Icariin attenuates renal interstitial fibrosis through G protein-coupled estrogen receptor in a UUO murine model.American journal of translational research · 2022Article
- The Relevant of Sex Hormone Levels and Acne Grades in Patients with Acne Vulgaris: A Cross-Sectional Study in Beijing.Clinical, cosmetic and investigational dermatology · 2022Article
- Castrated autoimmune glomerulonephritis mouse model shows attenuated glomerular sclerosis with altered parietal epithelial cell phenotype.Experimental biology and medicine (Maywood, N.J.) · 2021Article
- Gender Differences in Diabetic Kidney Disease: Focus on Hormonal, Genetic and Clinical Factors.International journal of molecular sciences · 2021Review
- Nuclear receptors in the kidney during health and disease.Molecular aspects of medicine · 2021Review
- Proximal tubular epithelial insulin receptor mediates high-fat diet-induced kidney injury.JCI insight · 2021Article
- Network Pharmacology-Based Prediction of Mechanism of Shenzhuo Formula for Application to DKD.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Estrogen and estrogen receptors in kidney diseases.Renal failure · 2021Review
- Evidence for G-Protein-Coupled Estrogen Receptor as a Pronatriuretic Factor.Journal of the American Heart Association · 2020Article
Corrections and comments
- Commented on by
- Erratum issuedErratum.2017
Authors and funding
10 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetes is manifested predominantly in males in experimental models, and compelling evidence suggests that 17β-estradiol (E2) supplementation improves hyperglycemia in humans. We previously generated a severely diabetic transgenic (Tg) mouse model by β-cell–specific overexpression of inducible cAMP early repressor (ICER) and found that male but not female ICER-Tg mice exhibit sustained hyperglycemia and develop major clinical and pathologic features of human diabetic nephropathy (DN). Thus, we hypothesized that differences in circulating hormone levels have a key role in determining susceptibility to diabetes. Here, we examined whether DN in male ICER-Tg mice is rescued by adjusting the androgen-to-E2 ratio to approximate that in normoglycemic female ICER-Tg mice. We treated hyperglycemic male ICER-Tg mice with orchiectomy (ORX), E2 pellet implantation, or both. E2 pellet implantation at an early stage of DN with or without ORX caused a rapid drop in blood glucose and a dramatic increase in β-cell number, and it markedly inhibited DN progression [namely, E2 reduced glomerulosclerosis, collagen 4 deposition and albuminuria, and prevented hyperfiltration]. Furthermore, E2 pellet implantation was more effective than ORX alone and induced a remarkable improvement, even when initiated at advanced-stage DN. In contrast, induction of normoglycemia by islet transplant in ICER-Tg mice eliminated albuminuria but was less effective than E2 + ORX in reducing glomerulosclerosis, collagen 4 deposition, and hyperfiltration. These findings indicate that E2 treatment is effective, even after establishment of DN, whereas glucose normalization alone does not improve sclerotic lesions. We propose that E2 intervention is a potential therapeutic option for DN.
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