The differential effects of stanozolol on human skin and synovial fibroblasts in vitro: DNA synthesis and receptor binding.

Agents Actions. 1994 Mar;41(1-2):37-43.

The differential effects of stanozolol on human skin and synovial fibroblasts in
vitro: DNA synthesis and receptor binding.

Ellis AJ, Cawston TE, Mackie EJ.

Rheumatology Research Unit, Addenbrooke's Hospital, Cambridge, UK.

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.