ArticleAmerican journal of physiology. Renal physiology2016
Klotho/fibroblast growth factor 23- and PTH-independent estrogen receptor-α-mediated direct downregulation of NaPi-IIa by estrogen in the mouse kidney.
Article in American journal of physiology. Renal physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Article
- Steroid hormones and nephrolithiasis: regulation of urine components metabolism and inflammation.Biology of sex differences · 2026Review
- Estrogen Treatment Lowers the Risk of Complications in Menopausal Women with Mild Burn Injury.Medicina (Kaunas, Lithuania) · 2025Article
- Phosphorous intake in foods and phosphorus status markers in circulation in the Boston Puerto Rican Health Study.Journal of food composition and analysis : an official publication of the United Nations University, International Network of Food Data Systems · 2024Article
- The basics of phosphate metabolism.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Review
- Expression of Renal Vitamin D and Phosphatonin-Related Genes in a Sheep Model of Osteoporosis.Animals : an open access journal from MDPI · 2021Article
- Estrogen inhibits renal Na-Pi Co-transporters and improves klotho deficiency-induced acute heart failure.Redox biology · 2021Article
- Clinicopathological and Prognostic Significance of Klotho and Estrogen Receptors Expression in Human Hepatocellular Carcinoma.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2021Article
- Article
- Estrogen and estrogen receptors in kidney diseases.Renal failure · 2021Review
- Acetazolamide causes renalAmerican journal of physiology. Renal physiology · 2020Article
- Electrolyte Disorders Induced by Antineoplastic Drugs.Frontiers in oncology · 2020Review
- Yield of diagnostic tests in unexplained renal hypophosphatemia: a case series.BMC nephrology · 2018Article
- X-linked hypophosphatemia and growth.Reviews in endocrine & metabolic disorders · 2017Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Estrogen treatment causes renal phosphate (Pi) wasting and hypophosphatemia in rats and humans; however, the signaling mechanisms mediating this effect are still poorly understood. To determine the specific roles of estrogen receptor isoforms (ERα and ERβ) and the Klotho pathway in mediating these effects, we studied the effects of estrogen on renal Pi handling in female mice with null mutations of ERα or ERβ or Klotho and their wild type (WT) using balance studies in metabolic cages. Estrogen treatment of WT and ERβ knockout (KO) mice caused a significant reduction in food intake along with increased renal phosphate wasting. The latter resulted from a significant downregulation of NaPi-IIa and NaPi-IIc protein abundance. The mRNA expression levels of both transporters were unchanged in estrogen-treated mice. These effects on both food intake and renal Pi handling were absent in ERα KO mice. Estrogen treatment of Klotho KO mice or parathyroid hormone (PTH)-depleted thyroparathyroidectomized mice exhibited a significant downregulation of NaPi-IIa with no change in the abundance of NaPi-IIc. Estrogen treatment of a cell line (U20S) stably coexpressing both ERα and ERβ caused a significant downregulation of NaPi-IIa protein when transiently transfected with a plasmid containing full-length or open-reading frame (ORF) 3'-untranslated region (UTR) but not 5'-UTR ORF of mouse NaPi-IIa transcript. In conclusion, estrogen causes phosphaturia and hypophosphatemia in mice. These effects result from downregulation of NaPi-IIa and NaPi-IIc proteins in the proximal tubule through the activation of ERα. The downregulation of NaPi-IIa by estrogen involves 3'-UTR of its mRNA and is independent of Klotho/fibroblast growth factor 23 and PTH signaling pathways.
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