Androgen metabolic response to indomethacin and the alkaline phosphatase inhibitor levamisole in fibroblasts

Objectives: The aim of this investigation is to study the effects of indomethacin (I) and the alkaline phosphatase (ALP) inhibitor levamisole (L) on androgen 5alpha-reductase expression in gingival and periosteal fibroblasts, in the context of repair in the periodontium. Chronically inflamed human gingival fibroblasts (HGF) were used to demonstrate the comparative effects of L on HGF and human oral periosteal fibroblasts (HPF). Material and Methods: Monolayer cultures of six cell lines of HPF of the fifth to ninth passage were incubated in duplicate with 14C-testosterone/14C-4-androstenedione as substrates in Eagle's MEM; I was added at concentrations of 1 and 3 mug/ml in the presence or absence of the established inhibitory concentration of 30 mug/ml L and incubated for 24 h. The medium was solvent extracted for radioactive metabolites, separated by thin layer chromatography and quantified. Results: L caused 50% inhibition of 5alpha-reductase and 17beta-hydroxysteroid dehydrogenase activity in HGF. In HPF, 5alpha-reductase expression was enhanced by I with both substrates, by 65-76% (n=6; p<0.01), inhibited by 30-50% (n=6; p<0.01) with L and restored to control values in combination. Conclusion: Yields of androgen metabolites may be linked to ALP activity, with implications on healing, during adjunctive treatment of inflammatory periodontal disease with I.