• Media type: E-Article
  • Title: The Unexpected Anabolic Phenotype and Extended Longevity of Skin Fibroblasts after Chronic Glucocorticoid Excess
  • Contributor: Pratsinis, Harris; Tsagarakis, Stylianos; Zervolea, Irene; Stathakos, Dimitri; Thalassinos, Nikos; Kletsas, Dimitris
  • imprint: SAGE Publications, 2006
  • Published in: Dose-Response
  • Language: English
  • DOI: 10.2203/dose-response.05-007.pratsinis
  • ISSN: 1559-3258
  • Keywords: Chemical Health and Safety ; Health, Toxicology and Mutagenesis ; Public Health, Environmental and Occupational Health ; Toxicology
  • Origination:
  • Footnote:
  • Description: <jats:p> Intense stress can challenge tissue homeostasis and accelerate the ageing process. However, several lines of evidence indicate that repeated mild stresses can have beneficial and even life-prolonging effects. Hypersecretion of glucocorticoids (GC) represents the major hormonal response to stress. Besides its life-sustaining role, GC excess, usually due to several side-effects that promote a “catabolic” phenotype, can be detrimental for several tissues. Cushing's syndrome patients are characterized by chronic endogenous GC excess and consequently at the time of diagnosis they have an atrophic elderly-like skin. Interestingly, when Cushing's syndrome fibroblasts were removed from the high-GC milieu in vivo and cultured in vitro under standard conditions they express an “anabolic” phenotype, i.e. they restore their ability for collagen synthesis, they secrete reduced levels of metalloproteases (MMP-1 and MMP-2) and have an increased proliferative capacity and contractility. Furthermore, these cells exhibit a significant extension of their proliferative lifespan, while they respond better to exogenous stress by producing significantly higher levels of heat-shock protein-70 (HSP70). These results imply that long-term hypercortisolism in vivo can have beneficial consequences on fibroblast physiology in vitro. </jats:p>
  • Access State: Open Access