Physiologically active androgens and growth factors contribute to healing responses by a variety of mechanisms, including stimulation of enzymes associated with matrix turnover. Some of these effects may be partially negated by nicotine. Both androgens and growth factors are able to compensate for oxidative effects induced by nicotine, being a significant deterrent to wound healing. The aim of this investigation is to establish the metabolic yields of androgen biomarkers in response to serial concentrations of nicotine (100, 500 and 1000 micrograms /ml), transforming growth factor beta (TGF, 10ng/ml) and insulin like growth factor (IGF, 20ng/ml), as an index of healing, using human gingival fibroblasts in culture (local Ethical committee approval obtained). Monolayer cultures of human gingival fibroblasts were established in Eagle's MEM. Duplicate incubations were performed using 14C-testosterone as substrate, in the presence or absence of serial concentrations of nicotine (100, 500 and 1000 micrograms / ml), TGF / IGF alone and in combinations of nicotine and growth factor. After a 24h incubation period, the medium was solvent extracted for metabolites, which were separated by thin layer chromatography and quantified using a radioisotope scanner. Serial concentrations of nicotine caused 40-90% reductions in the yields of DHT and 4-androstenedione. Optimal concentrations of TGF and IGF increased the yields of DHT and 4-androstenedione by 30-50%. When serial concentrations of nicotine were combined with growth factors, the yields of DHT were significantly less inhibited and the yields of 4-androstenedione were significantly stimulated (n=6; p<0.01). The bio-availability of growth factors could influence parameters of wound healing in an environment exposed to nicotine.
03 - 05 Nov 2003
Society for Endocrinology