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      Estrogens and aging skin

      *

      Dermato-endocrinology

      Landes Bioscience

      estrogen, skin, menopause, phytoestrogen, SERMs, aging, wound healing,

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          Abstract

          Estrogen deficiency following menopause results in atrophic skin changes and acceleration of skin aging. Estrogens significantly modulate skin physiology, targeting keratinocytes, fibroblasts, melanocytes, hair follicles and sebaceous glands, and improve angiogenesis, wound healing and immune responses. Estrogen insufficiency decreases defense against oxidative stress; skin becomes thinner with less collagen, decreased elasticity, increased wrinkling, increased dryness and reduced vascularity. Its protective function becomes compromised and aging is associated with impaired wound healing, hair loss, pigmentary changes and skin cancer.

           

          Skin aging can be significantly delayed by the administration of estrogen. This paper reviews estrogen effects on human skin and the mechanisms by which estrogens can alleviate the changes due to aging. The relevance of estrogen replacement, selective estrogen receptor modulators (SERMs) and phytoestrogens as therapies for diminishing skin aging is highlighted. Understanding estrogen signaling in skin will provide a basis for interventions in aging pathologies.

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          Most cited references 77

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          Differential ligand activation of estrogen receptors ERalpha and ERbeta at AP1 sites.

          The transactivation properties of the two estrogen receptors, ERalpha and ERbeta, were examined with different ligands in the context of an estrogen response element and an AP1 element. ERalpha and ERbeta were shown to signal in opposite ways when complexed with the natural hormone estradiol from an AP1 site: with ERalpha, 17beta-estradiol activated transcription, whereas with ERbeta, 17beta-estradiol inhibited transcription. Moreover, the antiestrogens tamoxifen, raloxifene, and Imperial Chemical Industries 164384 were potent transcriptional activators with ERbeta at an AP1 site. Thus, the two ERs signal in different ways depending on ligand and response element. This suggests that ERalpha and ERbeta may play different roles in gene regulation.
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            Role of antioxidants in the skin: anti-aging effects.

            Intracellular and extracellular oxidative stress initiated by reactive oxygen species (ROS) advance skin aging, which is characterized by wrinkles and atypical pigmentation. Because UV enhances ROS generation in cells, skin aging is usually discussed in relation to UV exposure. The use of antioxidants is an effective approach to prevent symptoms related to photo-induced aging of the skin. In this review, the mechanisms of ROS generation and ROS elimination in the body are summarized. The effects of ROS generated in the skin and the roles of ROS in altering the skin are also discussed. In addition, the effects of representative antioxidants on the skin are summarized with a focus on skin aging. 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
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              Coregulator function: a key to understanding tissue specificity of selective receptor modulators.

              Ligands for the nuclear receptor superfamily control many aspects of biology, including development, reproduction, and homeostasis, through regulation of the transcriptional activity of their cognate receptors. Selective receptor modulators (SRMs) are receptor ligands that exhibit agonistic or antagonistic biocharacter in a cell- and tissue context-dependent manner. The prototypical SRM is tamoxifen, which as a selective estrogen receptor modulator, can activate or inhibit estrogen receptor action. SRM-induced alterations in the conformation of the ligand-binding domains of nuclear receptors influence their abilities to interact with other proteins, such as coactivators and corepressors. It has been postulated, therefore, that the relative balance of coactivator and corepressor expression within a given target cell determines the relative agonist vs. antagonist activity of SRMs. However, recent evidence reveals that the cellular environment also plays a critical role in determining SRM biocharacter. Cellular signaling influences the activity and subcellular localization of coactivators and corepressors as well as nuclear receptors, and this contributes to gene-, cell-, and tissue-specific responses to SRM ligands. Increased understanding of the effect of cellular environment on nuclear receptors and their coregulators has the potential to open the field of SRM discovery and research to many members of the nuclear receptor superfamily.
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                Author and article information

                Journal
                Dermatoendocrinol
                Dermatoendocrinol
                DERM
                Dermato-endocrinology
                Landes Bioscience
                1938-1972
                1938-1980
                01 April 2013
                01 April 2013
                01 April 2013
                : 5
                : 2
                : 264-270
                Affiliations
                Centre for Skin Sciences; University of Bradford; Bradford, UK
                Author notes
                [* ]Correspondence to: M. Julie Thornton, Email: M.J.Thornton@ 123456bradford.ac.uk
                Article
                2012DE0194R 23872
                10.4161/derm.23872
                3772914
                Copyright © 2013 Landes Bioscience

                This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

                Categories
                Review

                Dermatology

                wound healing,, aging, serms, phytoestrogen, menopause, skin, estrogen

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