Abstract
The post-menopausal decrease in estrogen circulating levels results in rapid skin deterioration pointing out to a protective effect exerted by these hormones. The identity of the skin cell type responding to estrogens is unclear as are the cellular and molecular processes they elicit. Here, we reported that lack of estrogens induces rapid re-organization of the human dermal fibroblast cytoskeleton resulting in striking cell shape change. This morphological change was accompanied by a spatial re-organization of focal adhesion and a substantial reduction of their number as evidenced by vinculin and actin co-staining. Cell morphology and cytoskeleton organization was fully restored upon 17β-estradiol (E2) addition. Treatment with specific ER antagonists and cycloheximide respectively showed that the E2 acts independently of the classical Estrogen Receptors and that cell shape change is mediated by non-genomic mechanisms. E2 treatment resulted in a rapid and transient activation of ERK1/2 but not Src or PI3K. We show that human fibroblasts express the non-classical E2 receptor GPR30 and that its agonist G-1 phenocopies the effect of E2. Inhibiting GPR30 through treatment with the G-15 antagonist or specific shRNA impaired E2 effects. Altogether, our data reveal a novel mechanism by which estrogens act on skin fibroblast by regulating cell shape through the non-classical G protein-coupled receptor GPR30 and ERK1/2 activation.
Highlights
Skin exhibits several functions providing protection against pathogens and ultraviolet irradiation, regulating hydration and temperature, exerting immunological surveillance and displaying endocrine activities
Taken together these results demonstrate that the conventional estrogen receptors do not mediate the effects of 17β-estradiol on cell shape change of dermal fibroblasts
In this report we show that estrogens induce actin cytoskeleton remodelling in isolated human dermal fibroblasts through an Estrogen Receptor (ER)-independent, GPR30-dependent, non-genomic mechanism
Summary
Skin exhibits several functions providing protection against pathogens and ultraviolet irradiation, regulating hydration and temperature, exerting immunological surveillance and displaying endocrine activities. Altered structure and reduced function of both epidermis and dermis are attributable to aging and result in skin deterioration, in the face This is characterized by dryness, atrophy, fragility, loss of elasticity, increased extensibility and wrinkling, as well as impaired wound healing. ER interacts with proteins such as PI3K or Src and induces secondary cascades that may culminate into the regulation of gene expression, not via direct binding of ER to chromatin (reviewed in [23]) Since both genomic and non-genomic effects of estrogens depend on ER proteins, they can be blocked by ICI182,780, a synthetic compound that antagonizes estrogen binding to the receptors. We show that 17β-estradiol induces rapid cytoskeleton remodeling in isolated human dermal fibroblasts in primary cultures This occurs through a GPR30-dependent, ER-independent pathway that lead to ERK1/2, but not Src/PI3K, activation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
