Phenytoin (Ph) causes gingival overgrowth in inflamed gingivae. Androgen metabolism could be influenced by alkaline phosphatase activity and inhibited by the alkaline phosphatase inhibitor levamisole (L). In view of the anabolic role of the androgen metabolite 5alpha dihydrotestosterone (DHT), the aim of this investigation is to study the effects of Ph, histamine (H) and the alkaline phosphatase inhibitor levamisole (L) on the metabolism of androgen substrates by human gingival fibroblasts (approved by the local Ethics Committee). Confluent cultures of fibroblasts were incubated in Eagle's MEM with 14C-testosterone / 14C-4-androstenedione as substrates. Ph, H and L were added to the incubation at concentrations of 1,8 and 30 micrograms/ml, alone or in combinations of Ph+H and Ph+L. After 24h, the medium was solvent extracted, steroid metabolites separated by thin layer chromatography and quantified using a radioisotope scanner. The yields of DHT were enhanced by 60% and 50% respectively in response to H and Ph over control values (n=6; p<0.01). The combination of Ph and H also significantly stimulated DHT synthesis by 47%, but to a lesser extent than the individual incubations. L reduced DHT yields by 44% (n=6; p<0.01), while Ph in combination with L caused less inhibition over controls of 28% (n=6; p<0.01). Formation of DHT can be influenced by alkaline phosphatase and inhibited by levamisole. An increase in DHT in response to Ph and H could contribute to gingival overgrowth in inflamed gingivae.
03 - 04 Dec 2001
Society for Endocrinology