Journal article
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
Molecular and cellular endocrinology, Vol.382(2), pp.950-959
02/15/2014
DOI: 10.1016/j.mce.2013.11.005
PMID: 24239983
Abstract
•GPER-1 is topographically distributed in the epithelia of renal tubules.•GPER-1 specifically binds to estrogen but not to aldosterone.•The expression and subcellular localization of GPER-1 are regulated during the estrus cycle.
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 [3H]-17β-estradiol ([3H]-E2) binding, but no specific [3H]-aldosterone binding. In contrast, cytosolic preparations exhibited specific binding to [3H]-aldosterone but not to [3H]-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 [3H]-E2 binding to membranes of HEK-GPER-1 cells. Furthermore, aldosterone did not increase [35S]-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.
Details
- Title: Subtitle
- 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
- Creators
- Shi-Bin Cheng - Division of Hematology & Oncology, Rhode Island Hospital, Alpert Medical School of Brown University, RI, United StatesJing Dong - Marine Science Institute, University of Texas at Austin, Port Aransas, TX, United StatesYefei Pang - Marine Science Institute, University of Texas at Austin, Port Aransas, TX, United StatesJessica LaRocca - Department of Pathology and Laboratory Medicine, Rhode Island Hospital, Alpert Medical School of Brown University, RI, United StatesMary Hixon - Department of Pathology and Laboratory Medicine, Rhode Island Hospital, Alpert Medical School of Brown University, RI, United StatesPeter Thomas - Marine Science Institute, University of Texas at Austin, Port Aransas, TX, United StatesEdward J Filardo - Division of Hematology & Oncology, Rhode Island Hospital, Alpert Medical School of Brown University, RI, United States
- Resource Type
- Journal article
- Publication Details
- Molecular and cellular endocrinology, Vol.382(2), pp.950-959
- Publisher
- Elsevier Ireland Ltd
- DOI
- 10.1016/j.mce.2013.11.005
- PMID
- 24239983
- ISSN
- 0303-7207
- eISSN
- 1872-8057
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: RO1 CA119165, R01 ESO 12961
- Language
- English
- Date published
- 02/15/2014
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Surgery; Internal Medicine
- Record Identifier
- 9984051727302771
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