The differential responses of human skin and synovial fibroblasts to stanozolol in vitro: production of prostaglandin E2 and matrix metalloproteinases.
The anabolic steroid, stanozolol, is used therapeutically to treat a number of pathological conditions and its clinical effects suggest that it can modulate connective tissue breakdown. The ability of this compound to stimulate prostaglandin E2 (PGE2), collagenase, gelatinase and stromelysin production by human synovial and skin fibroblasts in vitro was examined. The results showed that stanozolol significantly stimulated, in a dose dependent manner, PGE2, collagenase and stromelysin production by skin fibroblasts. However, no stimulation was seen in the synovial cell lines. In contrast, no effect on gelatinase production was seen in either cell type, following exposure to stanozolol. The synovial and skin lines both exhibited a significant stimulation of PGE2 and all three metalloproteinases in response to interleukin-1 beta (IL-1 beta). The anabolic steroids nortestosterone and oxymetholone demonstrated no ability to stimulate PGE2 or collagenase production in either skin or synovial fibroblasts. These results suggest that stanozolol exerts differential effects on skin and synovial fibroblasts in vitro which may enable the elucidation of the mechanism of action of the compound in vivo.
Ellis
A J
AJ
Rheumatology Research Unit, Addenbrooke's Hospital, Cambridge, U.K.
Wright
J K
JK
Cawston
T E
TE
Hazleman
B L
BL
D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis*; D005109:Extracellular Matrix / Q000201:enzymology*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000187:drug effects*; D009277:Nandrolone / Q000494:pharmacology; D010110:Oxymetholone / Q000494:pharmacology; D012867:Skin / Q000166:cytology / Q000187:drug effects*; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects*
D009277:Nandrolone; D008666:Metalloendopeptidases; D015232:Dinoprostone; D010110:Oxymetholone