Anatomical location and redistribution of G protein-coupled estrogen receptor-1 during the estrus cycle in mouse kidney and specific binding to estrogens but not aldosterone
| Autor: | Edward J. Filardo, Peter Thomas, Jessica LaRocca, Mary L. Hixon, Jing Dong, Yefei Pang, Shi-Bin Cheng |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
medicine.drug_class Spironolactone Biology Biochemistry Receptors G-Protein-Coupled Mice chemistry.chemical_compound Endocrinology Mineralocorticoid receptor Estrus Internal medicine medicine Loop of Henle Animals Humans Estrogen binding Kidney Tubules Distal Aldosterone Molecular Biology Mineralocorticoid Receptor Antagonists Kidney Estradiol Reproduction Estradiol binding Eplerenone Low Density Lipoprotein Receptor-Related Protein-2 HEK293 Cells Receptors Mineralocorticoid medicine.anatomical_structure Gene Expression Regulation Receptors Estrogen chemistry Guanosine 5'-O-(3-Thiotriphosphate) Estrogen G-Protein Coupled Estrogen Receptor 1 Female Protein Binding |
| Zdroj: | Molecular and Cellular Endocrinology. 382:950-959 |
| ISSN: | 0303-7207 |
| DOI: | 10.1016/j.mce.2013.11.005 |
| Popis: | Prior studies have linked renoprotective effects of estrogens to G-protein-coupled estrogen receptor-1 (GPER-1) and suggest that aldosterone may also activate GPER-1. Here, the role of GPER-1 in murine renal tissue was further evaluated by examining its anatomical distribution, subcellular distribution and steroid binding specificity. Dual immunofluorescent staining using position-specific markers showed that GPER-1 immunoreactivity primarily resides in distal convoluted tubules and the Loop of Henle (stained with Tamm-Horsfall Protein-1). Lower GPER-1 expression was observed in proximal convoluted tubules marked with megalin, and GPER-1 was not detected in collecting ducts. Plasma membrane fractions prepared from whole kidney tissue or HEK293 cells expressing recombinant human GPER-1 (HEK-GPER-1) displayed high-affinity, specific [(3)H]-17β-estradiol ([(3)H]-E2) binding, but no specific [(3)H]-aldosterone binding. In contrast, cytosolic preparations exhibited specific binding to [(3)H]-aldosterone but not to [(3)H]-E2, consistent with the subcellular distribution of GPER-1 and mineralocorticoid receptor (MR) in these preparations. Aldosterone and MR antagonists, spironolactone and eplerenone, failed to compete for specific [(3)H]-E2 binding to membranes of HEK-GPER-1 cells. Furthermore, aldosterone did not increase [(35)S]-GTP-γS binding to membranes of HEK-GPER-1 cells, indicating that it is not involved in G protein signaling mediated through GPER-1. During the secretory phases of the estrus cycle, GPER-1 is upregulated on cortical epithelia and localized to the basolateral surface during proestrus and redistributed intracellularly during estrus. GPER-1 is down-modulated during luteal phases of the estrus cycle with significantly less receptor on the surface of renal epithelia. Our results demonstrate that GPER-1 is associated with specific estrogen binding and not aldosterone binding and that GPER-1 expression is modulated during the estrus cycle which may suggest a physiological role for GPER-1 in the kidney during reproduction. |
| Databáze: | OpenAIRE |
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