Modulation of androgen metabolism by phenytoin,oestradiol and tamoxifen in human gingival fibroblasts

OBJECTIVES: The aim of this investigation is to study androgen metabolism in gingival fibroblasts in response to phenytoin, oestradiol and the antioestrogen tamoxifen, in order to establish the possible role of hormones in the aetiopathogenesis of phenytoin-induced gingival overgrowth. MATERIALS AND METHODS: Six cell lines of human gingival fibroblasts were established in monolayer culture in Eagle's minimum essential medium. Duplicate incubations were performed independently with radiolabelled testosterone and 4-androstenedione, respectively (14C-T/14C-4-A), with optimal concentrations of phenytoin, oestradiol and tamoxifen alone and in combination. At the end of a 24-h incubation period, the medium was solvent extracted for steroid metabolites, which were separated by thin layer chromatography and quantified using a radioisotope scanner. RESULTS: The substrates were metabolised mainly to the diols, 5alpha-dihydrotestosterone (DHT) and 4-androstenedione or testosterone, with the two substrates used. The trends were that phenytoin and oestradiol significantly elevated the yields of the androgens DHT, diols and 4-A/testosterone from both substrates while tamoxifen inhibited the stimulatory effects of oestradiol and phenytoin alone and in combination (n=6; p<0.01, one-way anova). CONCLUSION: Specific hormone-mediated activity in response to phenytoin could contribute to the pathogenesis of gingival overgrowth, which can be decreased by the anti oestrogen tamoxifen.