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Questions About Steroids
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Topic starter
19/09/2019 11:23 am
Ann N Y Acad Sci. 2007 Apr;1100:449-54.
Prior chronic in vivo glucocorticoid excess leads to an anabolic phenotype and an extension of cellular life span of skin fibroblasts in vitro.
Kletsas D, Pratsinis H, Gioni V, Pilichos K, Yiacoumettis AM, Tsagarakis S.
Laboratory of Cell Proliferation and Ageing, Institute of Biology, National Centre for Scientific Research Demokritos, 15310 Athens, Greece.
Intense stress can be detrimental for tissue homeostasis and accelerates aging. On the other hand, repeated mild stresses can have beneficial and even life-prolonging effects. Hypersecretion of glucocorticoids (GCs) represents the major hormonal response to stress. However, besides its life-sustaining role, GC excess can promote a "catabolic" phenotype. Accordingly, we have studied the effect of long-lasting exposure to high GC levels in vivo on several parameters of tissue homeostasis, as well as cellular senescence, in cells removed from the high-GC milieu in vivo and then cultured in vitro. To this end, we have used human skin fibroblasts from (a) Cushing's syndrome patients that are characterized by chronic endogenous GC excess and (b) patients treated with exogenous GC administration. Interestingly, when Cushing's syndrome fibroblasts were cultured in vitro under standard conditions they express an "anabolic" phenotype, i.e., they restore their ability for collagen synthesis, secrete reduced levels of metalloproteases, and have an increased proliferative capacity and contractility. Furthermore, these cells exhibit a significant extension of their proliferative life span, while they respond better to exogenous stress by producing significantly higher levels of heat-shock protein-70 (HSP70). In addition, preliminary results with fibroblasts from patients subjected to chronic exogenous GC administration indicate that they express a similar behavior in vitro, at least with regard to the restoration of collagen expression. These data suggest that prior exposure to elevated GC concentrations is not associated with persisting adverse effects on fibroblasts and may also have a beneficial outcome in some aspects of cell physiology, including longevity in vitro.
dr frankenstein
Topic starter
19/09/2019 11:44 am
Eur J Endocrinol. 2000 May;142(5):472-6.
Decreased ligand affinity rather than glucocorticoid receptor down-regulation in patients with endogenous Cushing's syndrome.
Huizenga NA, De Herder WW, Koper JW, de Lange P, v D Lely AJ, Brinkmann AO, de Jong FH, Lamberts SW.
Department of Internal Medicine III, Dijkzigt University Hospital Rotterdam, Dr Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
OBJECTIVE: Glucocorticoids (GCs) serve a variety of important functions throughout the body. The synthesis and secretion of GCs are under the strict influence of the hypothalamo-pituitary-adrenal axis. The mechanisms of action of GCs are mediated by the intracellular glucocorticoid receptor (GR). Over the years, many studies have been performed concerning the regulation of GR expression by GC concentrations. METHODS: In the present study, we determined the characteristics of the GR in peripheral mononuclear blood leukocytes (PBML) from thirteen patients with endogenous Cushing's syndrome and fifteen control subjects, using a whole cell dexamethasone binding assay. Furthermore, cortisol concentrations were determined in order to investigate a possible relationship between serum cortisol levels and receptor characteristics. RESULTS: There were no differences in mean receptor number between patients and controls. On the other hand, a significantly lower ligand affinity was identified in cells from patients with Cushing's syndrome compared with controls. A complete normalisation of the ligand affinity was observed after treatment in the only patient tested in this respect, whereas the receptor number was not affected. In patients, there was a statistically significant negative correlation between cortisol concentrations and ligand affinity, which was not found in controls. CONCLUSION: Receptor down-regulation does not occur in PBML from patients with endogenous Cushing's syndrome. On the other hand, there seems to be a diminished ligand affinity which possibly reflects receptor modification in response to exposure to the continuously high cortisol levels in patients with Cushing's syndrome. This assumption is substantiated by the fact that in one patient a normalisation of the ligand affinity after complete remission of the disease was seen.
dr frankenstein
19/09/2019 12:05 pm
I've doubted the alleged 'negative impact' of corticosteroids (particularly in guys on AAS) for years..
Topic starter
19/09/2019 12:29 pm
nice to hear.
dr frankenstein