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Cited by 10Estrogen and related hormone effectsConnexins and lens biologyReceptor Mechanisms and Signaling

High affinity nuclear and nongenomic estradiol binding sites in the human and mouse lens

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Kirker, M. Rachel, Gallagher, Katie M., Witt-Enderby, Paula A., Davis, Vicki L.·2013·Experimental Eye Research
DOI 10.1016/j.exer.2013.04.002PMC PMC3786782
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Abstract

Estrogen is reported to be protective against cataracts in women and animal models. Immunodetection methods have identified the classic estrogen receptors (ER), ERα and ERβ, in human lens epithelial cells and their RNAs have been detected in the rat and human lens. To verify that estrogen binding occurs in the lens, sensitive [(125)I]-17β-estradiol binding analyses were performed on subcellular lens fractions from women (ages 39-78 years). The presence of high affinity estradiol binding sites in the nuclear, cytoplasmic, and membrane fractions indicate the lens is able to respond to estrogens, even up to age 78, although fewer binding sites were detected in the postmenopausal women. Additionally, due to the importance of mouse models in estrogen action and lens research, lenses from intact female mice were also analyzed. Both the C57BL/6 and FVB/N mouse strains also possessed high affinity binding sites in all three lens fractions. Furthermore, transcripts for ERα, ERβ, and G protein-coupled estrogen receptor (GPER; previously called GPR30) that bind estradiol with high affinity were expressed in the human and mouse lenses. These data provide the first evidence of GPER expression in the lens. Its role, functions, and subcellular location are currently unknown, but a G-shift assay in the membrane fractions of human and mouse lenses did not show evidence that estradiol induced classic G protein-coupled receptor activation. All three receptor transcripts were also detected in the lens capsule region isolated from female C57BL/6 mice, which is mainly comprised of epithelial cells. In contrast, only ERα and GPER were expressed in the cortex/nuclear region, which is primarily composed of differentiating and organelle-free fiber cells. No significant differences in specific estradiol binding and receptor RNA expression were observed in the lenses between male and female C57BL/6 mice. These findings indicate that the lens is an estrogen target tissue in both sexes. The identification of GPER, in addition to ERα and ERβ, in the lens also adds to the complexity of possible estrogen responses in the lens. Accordingly, the protective effects of estrogen in women and animals may be mediated by all three estrogen receptors in the lens. In addition, the similarities in binding and receptor RNA expression in the lenses of both species suggest that mice can be used to model estrogen action in the human lens.

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  • The biological effects of estrogen are mainly mediated via nuclear and membrane estrogen receptors (ERα, ERβ, and GPER), all three of which bind 17β-estradiol with high affinity in the low nM range.

    “The biological effects of estrogen are mainly mediated via nuclear and membrane estrogen receptors (ERs), including estrogen receptor α (ERα), estrogen receptor β (ERβ), and G-protein-coupled ER (GPR30 or GPER), all three bind 17β-estradiol with high affinity in the low nM range (118, 119).”

    From From mitochondria to sarcopenia: role of 17β-estradiol and testosterone (2023) · cites this paper as [118]

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Authors
Kirker, M. R., Gallagher, K. M., Witt-Enderby, P. A., & Davis, V. L.
Affiliations
Duquesne University (US)
Corresponding author
Davis, Vicki L.
ORCID
Gallagher, Katie M.
Venue
Experimental Eye Research
Publisher
Elsevier BV
Published
2013-07
Volume
112
Pages
1-9
ISSN
0014-4835 (ISSN-L)
DOI
10.1016/j.exer.2013.04.002
PMC
PMC3786782
OpenAlex
W2131736745
Cited by
10
References
57
Citations by year
2026: 1 · 2025: 1 · 2023: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2017: 2 · 2016: 1 · 2014: 1
FWCI
0.44
Type
journal article
Language
en
Open access
Locations
  • Experimental Eye Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Duquesne University
  • National Institutes of Health
  • National Eye Institute (R03EY014600, EY014600)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
estradiol binding sites, lens, estrogen receptor, estrogen receptor alpha, estrogen receptor beta, G protein-coupled estrogen receptor, GPR30, non-genomic estrogen signaling, cataract prevention, lens epithelial cells, lens capsule, lens fiber cells, postmenopausal women, estrogen target tissues, mouse model
MeSH terms
Adult, Aged, Aging, Animals, Binding Sites, Cell Membrane, Cell Nucleus, Cytoplasm, Estradiol, Female, Gene Expression Regulation, Humans, Lens, Crystalline, Male, Mice, Inbred C57BL, Middle Aged, Receptors, Estrogen, RNA, Messenger, Receptors, G-Protein-Coupled, Estrogen Receptor alpha, Estrogen Receptor beta, Mice, Real-Time Polymerase Chain Reaction

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