The anabolic role of androgens in growth and regeneration, has similar implications in periodontal tissues. Studies suggest that androgens and growth factors could affect activity of the enzyme alkaline phosphatase, being closely linked to anabolic effects on tissues matrices. Nicotine has detrimental effects on healing. One of the mechanisms involved is impairment of alkaline phosphatase activity. The aim of this investigation is to study the response of nicotine to platelet derived growth factor beta (PDGF) and the alkaline phosphatase inhibitor levamisole, using androgen metabolites as biomarkers of healing, in a human fibroblast model (obtained local Ethical committee approval). Monolayer cultures of human gingival fibroblasts (HGF) were prepared in multiwell dishes; 14C-testosterone was used as substrate in the presence or absence of optimal concentrations of nicotine(500 micrograms/ml), PDGF, levamisole (30 micrograms /ml) and their combinations, in Eagle's MEM for 24h. The medium was solvent extracted for isolation of metabolites. They were separated and quantified by thin layer chromatography and radioisotope scanning respectively. The main metabolites formed were 5 alpha dihydrotestosterone (DHT), 4-androstenedione and the diols. Nicotine and levamisole significantly reduced the yields of these metabolites by 2-4-fold and 20-36% respectively. PDGF enhanced the yield of diols, when combined with nicotine, which was reduced by levamisole (n=6; p<0.01, Wilcoxon signed rank statistic for paired observations). These findings indicate that the negative influence of nicotine on androgen metabolism may be exerted via decreased alkaline phosphatase activity, overcome by PDGF and negated by the ALP inhibitor levamisole. It is possible that the detrimental effect exerted by nicotine on fibroblasts, could impair wound healing partly by this mechanism .
03 - 05 Nov 2003
Society for Endocrinology