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Mol Cell Endocrinol. 2014 Feb 15;382(2):950-9. doi: 10.1016/j.mce.2013.11.005. Epub 2013 Nov 13.

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.

Author information

1
Division of Hematology & Oncology, Rhode Island Hospital, Alpert Medical School of Brown University, RI, United States.
2
Marine Science Institute, University of Texas at Austin, Port Aransas, TX, United States.
3
Department of Pathology and Laboratory Medicine, Rhode Island Hospital, Alpert Medical School of Brown University, RI, United States.
4
Marine Science Institute, University of Texas at Austin, Port Aransas, TX, United States. Electronic address: peter.thomas@utexas.edu.
5
Division of Hematology & Oncology, Rhode Island Hospital, Alpert Medical School of Brown University, RI, United States. Electronic address: ed@radixbiosolutions.com.

Abstract

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.

KEYWORDS:

Aldosterone binding; Distal convoluted tubules; Estradiol binding; Estrus cycle; GPER-1; Mineralocorticoid receptor

PMID:
24239983
DOI:
10.1016/j.mce.2013.11.005
[Indexed for MEDLINE]

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