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 prostagla ndin E(2) (PGE(2)) and the matrix metalloproteinases collagenase and s tromelysin in human skin fibroblasts but not in rheumatoid synovial fi broblasts. The basis for these differential responses was investigated at the levels of DNA synthesis and steroid receptor binding. Stanozol ol inhibited fibroblast growth factor (FGF)-stimulated DNA synthesis i n both the skin and synovial fibroblasts, showing that both cell types were capable of responding to the compound. Competitive binding assay s indicated that stanozolol bound specifically to both the skin and sy novial 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 co llagenase production in either cell type. Nortestosterone, dexamethaso ne and 17 beta-oestradiol had no effect on binding of stanozolol to ei ther cell type. These results indicate that the inhibition of DNA synt hesis by stanozolol is elicited through the progesterone receptor. The effects of stanozolol on collagenase and PGE(2) production are mediat ed by a different receptor, present on skin but not synovial fibroblas ts, and as yet unidentified.