The Unexpected Anabolic Phenotype and Extended Longevity of Skin Fibroblasts after Chronic Glucocorticoid Excess

• Published in: Dose-response 2006-08, Vol.4 (2), p.133-144
• Main Authors: Pratsinis, Harris, Tsagarakis, Stylianos, Zervolea, Irene, Stathakos, Dimitri, Thalassinos, Nikos, Kletsas, Dimitris
• Format: Article
• Language: English
• ISSN: 1559-3258; 1559-3258
• DOI: 10.2203/dose-response.05-007.Pratsinis

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.