ArticleAmerican journal of physiology. Renal physiology2015
Estrogen directly and specifically downregulates NaPi-IIa through the activation of both estrogen receptor isoforms (ERα and ERβ) in rat kidney proximal tubule.
Article in American journal of physiology. Renal physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Aromatase enzyme: Paving the way for exploring aromatization for cardio-renal protection.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Pooled it
- Steroid hormones and nephrolithiasis: regulation of urine components metabolism and inflammation.Biology of sex differences · 2026Review
- The double-edged sword effect of estrogen in kidney disease and its precision modulation.Frontiers in endocrinology · 2026Review
- Identification of a Novel HomozygousInternational journal of molecular sciences · 2025Article
- Aromatase inhibition increases blood pressure and markers of renal injury in female rats.American journal of physiology. Renal physiology · 2022Article
- Estrogen inhibits renal Na-Pi Co-transporters and improves klotho deficiency-induced acute heart failure.Redox biology · 2021Article
- Nuclear receptors in the kidney during health and disease.Molecular aspects of medicine · 2021Review
- A single dose of estrogen during hemorrhagic shock protects against Kidney Injury whereas estrogen restoration in ovariectomized mice is ineffective.Scientific reports · 2020Article
- Acetazolamide causes renalAmerican journal of physiology. Renal physiology · 2020Article
- Estrogen receptor alpha expression in renal tissue and its relationship with prognosis in immunoglobulin A nephropathy.International journal of clinical and experimental pathology · 2020Article
- Mechanisms of phosphate transport.Nature reviews. Nephrology · 2019Review
- Yield of diagnostic tests in unexplained renal hypophosphatemia: a case series.BMC nephrology · 2018Article
- Mendelian randomization analysis indicates serum urate has a causal effect on renal function in Chinese women.International urology and nephrology · 2017Article
- Klotho/fibroblast growth factor 23- and PTH-independent estrogen receptor-α-mediated direct downregulation of NaPi-IIa by estrogen in the mouse kidney.American journal of physiology. Renal physiology · 2016Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
We have previously demonstrated that estrogen (E2) downregulates phosphate transporter NaPi-IIa and causes phosphaturia and hypophosphatemia in ovariectomized rats. In the present study, we examined whether E2 directly targets NaPi-IIa in the proximal tubule (PT) and studied the respective roles of estrogen receptor isoforms (ERα and ERβ) in the downregulation of NaPi-IIa using both in vivo and an in vitro expression systems. We found that estrogen specifically downregulates NaPi-IIa but not NaPi-IIc or Pit2 in the kidney cortex. Proximal tubules incubated in a "shake" suspension with E2 for 24 h exhibited a dose-dependent decrease in NaPi-IIa protein abundance. Results from OVX rats treated with specific agonists for either ERα [4,4',4″;-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol, PPT] or ERβ [4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol, DPN] or both (PPT + DPN), indicated that only the latter caused a sharp downregulation of NaPi-IIa, along with significant phosphaturia and hypophosphatemia. Lastly, heterologous expression studies demonstrated that estrogen downregulated NaPi-IIa only in U20S cells expressing both ERα and ERβ, but not in cells expressing either receptor alone. In conclusion, these studies demonstrate that rat PT cells express both ERα and ERβ and that E2 induces phosphaturia by directly and specifically targeting NaPi-IIa in the PT cells. This effect is mediated via a mechanism involving coactivation of both ERα and ERβ, which likely form a functional heterodimer complex in the rat kidney proximal tubule.
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