Summary
Confluent cultures of normal primary human skin fibroblasts were incubated with various glucocorticosteroids which are in current use clinically for the treatment of various skin disorders. For all steroids concentrations were found at which collagen hydroxyproline formation was inhibited, while total protein synthesis was little affected. The concentration effective for inhibition was highest for hydrocortisone and lowest for clobetasol-17-propionate. All other steroids (hydrocortisone-17-butyrate, triamcinolone acetonide and betamethasone-17-valerate) showed medium effectiveness. Fluorination as such was not a factor in the degree of inhibition. The inhibition observed was shown to be independent of concomitant specific effects on cell proliferation or cell turnover. The possible implications of these findings on the therapeutic effects in psoriasis and the frequently occurring atrophic side-effects of these steroids are discussed.
Zusammenfassung
Konfluente Zellkulturen normaler primärer menschlicher Hautfibroblasten wurden mit einer Anzahl Glucocorticosteroide inkubiert, die gegenwärtig in der Klinik zur Behandlung zahlreicher Hauterkrankungen verwendet werden. Bei allen diesen Steroiden gab es Konzentrationen, die die Synthese des Hydroxyprolins in Kollagen hemmten, während die Synthese des Gesamtproteins kaum beeinflußt wurde. Die zur Hemmung erforderliche Konzentration war für Hydrocortison am höchsten und für Clobetasol-17-propionat am niedrigsten. Die Hemmung durch die anderen Steroide (Hydrocortison-17-butyrat, Triamcinolon-acetonid und Betamethason-17-valerat) erfolgte im Zwischenbereich. Die Hemmung wurde durch Fluorinierung an sich nicht beeinflußt und wurde auch nicht durch spezifische Effekte auf die Zellvermehrung oder den Zell-turnover verursacht. Die möglichen Beziehungen wurden diskutiert zwischen diesen Ergebnissen und den therapeutischen Effekten der hier untersuchten Steroide bei Psoriasis, sowie die öfters gefundenen atrophischen Seiteneffekten.
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References
Bachra, B. N., van der Eb, A. J.: Site of proline hydroxylation during collagen synthesis in mouse fibroblasts. Biochem.9, 3001–3011 (1970)
Burton, K.: A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem. J.62, 315–323 (1956)
Castor, C. W.: Adrenocorticoid suppression of mucopolysaccharide formation in human connective tissue cell cultures. J. Lab. Clin. Med.60, 788–798 (1962)
Castor, C. W.: Regulation of collagen and hyaluronate formation in human synovial fibroblast cultures. J. Lab. Clin. Med.75, 798–810 (1970)
Cunningham, D. D., Trash, C. R., Glynn, R. D.: Initiation of division of density-inhibited fibroblasts by glucocorticoids. In: Control of proliferation in animal cells. (Eds.) B. Clarkson, R. Baserga. Cold Spring Harbor Conferences on cell proliferation 1974
Cutroneo, K. R., Costello, D., Fuller, G. C.: Alteration of proline hydroxylase activity by glucocorticoids. Molec. Pharmac.20, 2797–2804 (1971)
Cutroneo, K. R., Counts, D. F.: Anti-inflammatory steroids and collagen metabolism: Glucocorticoid-mediated alterations of prolyl hydroxylase activity and collagen synthesis. Molec. Pharm.11, 632–639 (1975)
Cutroneo, K. R., Stassen, F. L. H., Cardinale, G. J.: Anti-inflammatory steroids and collagen metabolism: Glucocorticoid-mediated decrease of prolyl hydroxylase. Molec. Pharm.11, 44–51 (1975)
Ebert, P. S., Prockop, D. J.: Influence of cortisol on the synthesis of sulfated mucopolysaccharides and collagen in chick embryos. Biochem. Biophys. Acta136, 45–55 (1967)
Hermanns, J. F.: Etude comparative de l'ultrastructure du derme au cours du vieillissement et de la corticothérapie. Symposium «Corticothérapie locale», pp. 149–157. Brussels: Brocades-Belga 1976
Koob, T. J., Jeffrey, J. J., Eisen, A. Z.: Regulation of human skin collagenase activity by hydrocortisone and dexamethasone in organ culture. Biochem. Biophys. Res. Comm.61, 1083–1088 (1974)
Manthorpe, R., Helin, G., Kofod, B., Lorenzen, I.: Effects of glucocorticosteroids on connective tissue of aorta and skin in rabbits. Acta Endocr.77, 310–324 (1974)
Piérard, G. E.: Microanatomie et propriétés fonctionnelles du tissu conjontif de la peau. Symposium «Corticothérapie Locale», pp. 135–148. Brussels: Brocades-Belga 1976
Ponec, M., de Haas, C., Bachra, B. N., Polano, M. K.: Effects of glucocorticosteroids on primary human skin fibroblasts. I. Arch. Derm. Res.259 (1977)
Uitto, J., Hannuksela, M.: Effect of topical betamethasone-17-valerate on collagen biosynthesis in psoriatic skin. Dermatologica (Basel)143, 184–189 (1971)
Uitto, J., Mustakallio, K. K.: Effect of hydrocortisone acetate, flucinolone acetonide, fluclorolone acetonide, betamethasone-17-valerate and fluprednyliden-21-acetate on collagen biosynthesis. Biochem. Pharm.20, 2495–2503 (1971)
Uitto, J., Teir, H., Mustakallio, K. K.: Corticosteroid-induced inhibition of the biosynthesis of human skin collagen. Biochem. Pharm.21, 2161–2167 (1972)
Zesch, A., Schaefer, H.: Penetrationskinetik von radiomarkierten Hydrocortison aus verschiedenartigen Salbengrundlagen in die menschliche Haut. II. In vivo. Arch. Derm. Forsch.252, 245–256 (1975)
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Ponec, M., Hasper, I., Vianden, G.D.N.E. et al. Effects of glucocorticosteroids on primary human skin fibroblasts. Arch. Derm. Res. 259, 125–134 (1977). https://doi.org/10.1007/BF00557952
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DOI: https://doi.org/10.1007/BF00557952