The anti-convulsant phenytoin stimulates matrix synthesis in inflamed gingivae. Oestrogen and androgen metabolites have anabolic effects on target tissue. The aim of this investigation is to study the effects of phenytoin on androgen metabolism in human gingival fibroblasts in response to oestradiol and the anti-androgen finasteride (approved by the local Ethics Committee). Monolayer cultures of human gingival fibroblasts were established in Eagle's MEM with 14C-testosterone and 1 microgram/ml of phenytoin (Ph), oestradiol (O) and finasteride (F) alone and in combinations of Ph+F, O+F. Similar incubations were performed with 14C-4-androstenedione (4-A) as substrate. After a 24h incubation period, the medium was solvent extracted with ethlyl acetate for steroid metabolites, which were separated using thin layer chromatography and quantified using a radioisotope scanner. There were 75% increases in the formation of DHT in response to Ph or O with 50% inhibition by finasteride (n=4; p<0.01). Ph or O in combination with F showed less inhibition than F alone. There was not much change in the metabolism to 4-A, while the formation of diols diminished in the finasteride incubations. Similar trends were seen with 14C-4-androstenedione as substrate. Gingival fibroblasts are androgen and oestrogen target cells; their metabolic response to phenytoin could be instrumental in contributing to phenytoin-induced gingival overgrowth.
03 - 04 Dec 2001
Society for Endocrinology