The differential effects of stanozolol on human skin and synovial fibroblasts in vitro: DNA synthesis and receptor binding.
The anabolic steroid stanozolol stimulates the production of prostaglandin E2 (PGE2) and the matrix metalloproteinases collagenase and stromelysin in human skin fibroblasts but not in rheumatoid synovial fibroblasts. The basis for these differential responses was investigated at the levels of DNA synthesis and steroid receptor binding. Stanozolol inhibited fibroblast growth factor (FGF)-stimulated DNA synthesis in both the skin and synovial fibroblasts, showing that both cell types were capable of responding to the compound. Competitive binding assays indicated that stanozolol bound specifically to both the skin and synovial fibroblasts. Binding of stanozolol to both cell types could be partially displaced by progesterone, indicating that stanozolol binds to the progesterone receptor. Immunocytochemical studies confirmed the presence of progesterone receptors on skin and synovial fibroblasts. However, progesterone failed to elicit any response with respect to collagenase production in either cell type. Nortestosterone, dexamethasone and 17 beta-oestradiol had no effect on binding of stanozolol to either cell type. These results indicate that the inhibition of DNA synthesis by stanozolol is elicited through the progesterone receptor. The effects of stanozolol on collagenase and PGE2 production are mediated by a different receptor, present on skin but not synovial fibroblasts, and as yet unidentified.
Ellis
A J
AJ
Rheumatology Research Unit, Addenbrooke's Hospital, Cambridge, UK.
Cawston
T E
TE
Mackie
E J
EJ
D001667:Binding, Competitive; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D009277:Nandrolone / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013197:Stanozolol / Q000494:pharmacology*; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D011980:Receptors, Progesterone; D011987:Receptors, Steroid; D011374:Progesterone; D013197:Stanozolol; D004958:Estradiol; D009277:Nandrolone; D003907:Dexamethasone; D004247:DNA; D007213:Indomethacin