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.