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Estrogen receptor beta is a novel therapeutic target for photoaging.
- Source :
-
Molecular pharmacology [Mol Pharmacol] 2010 May; Vol. 77 (5), pp. 744-50. Date of Electronic Publication: 2010 Jan 28. - Publication Year :
- 2010
-
Abstract
- One of the many harmful factors faced by the skin is solar UV radiation, which damages skin by inducing chronic low-grade inflammation through increased expression of proinflammatory cytokines, metalloproteinases (MMPs) and cyclooxygenase-2 (COX-2). Estrogen receptors (ERs) alpha and beta are ligand-dependent transcription factors that are expressed in skin, and an ERbeta agonist has previously shown efficacy in vivo in models of pain and inflammation. Because ERbeta does not carry the breast and uterine proliferation liabilities of ERalpha, we decided to explore the possibility of using ERbeta as a target for photoaging. We show that ERbeta-selective compounds suppressed the expression of cytokines and MMPs in activated keratinocytes and fibroblast-based in vitro models of photoaging. Furthermore, in activated dermal fibroblasts, ERbeta-selective compounds also inhibited COX-2. These activities of ERbeta ligands in skin cells correlated with the expression levels of ERbeta and showed reversal by treatment with a potent synthetic ER antagonist. Furthermore, the pharmacology of ERbeta-selective compound was observed in wild-type but not in skin cells obtained from ERbeta knockout mice. Finally, we demonstrate that a synthetic ERbeta agonist inhibited UV-induced photodamage and skin wrinkle formation in a murine model of photoaging. Therefore, the potential of an ERbeta ligand to regulate multiple pathways underlying the cause of photoaging suggests ERbeta to be a novel therapeutic target for the prevention and treatment of photoaging.
- Subjects :
- Aging radiation effects
Animals
Cytokines genetics
Estrogen Receptor beta deficiency
Estrogen Receptor beta drug effects
Estrogen Receptor beta genetics
Female
Fibroblasts physiology
Humans
Ligands
Matrix Metalloproteinases genetics
Mice
Mice, Hairless
Mice, Knockout
Skin Aging genetics
Skin Aging physiology
Sunlight adverse effects
Ultraviolet Rays adverse effects
Estrogen Receptor beta physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1521-0111
- Volume :
- 77
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 20110405
- Full Text :
- https://doi.org/10.1124/mol.109.062877