THE INFLUENCE OF INSULIN-LIKE GROWTH-FACTOR (IGF) ON C19 STEROID CONVERSIONS BY HUMAN GINGIVA AND IN CULTURED GINGIVAL FIBROBLASTS

THE METABOLIC CONVERSION OF 14C-testosterone by human gingival tissue in response to IGF was studied. Androgen metabolic studies were also p erformed in 5 to 7 cell-lines of cultured gingival fibroblasts, using 14C-testosterone and 14C-4-androstenedione as initial substrates. Dupl icate incubations of gingival tissue were performed after establishing the wet weight, in Eagle's MEM + 10% FCS and optimal stimulatory conc entrations of IGF for 24 hours. Similar incubations were performed in duplicate with cell-lines of gingival fibroblasts, control/IGF and 14C -testosterone/14C-4-androstenedione. At the end of the incubation peri od, the radioactive metabolites were extracted, evaporated, subjected to thin layer chromatography for their separation, and quantified by s canning in a Berthold's linear analyzer. With the gingival tissue samp les, IGF caused a 4-fold increase in 5 alpha-dihydrotestosterone (DHT) synthesis (n = 5; P < 0.1, Wilcoxon signed rank test for paired obser vations) and a 3.5-fold increase in LC-androstenedione formation (n = 5; P < 0.1) from 14C-testosterone. When similar incubations were perfo rmed with cell-lines of fibroblasts and 14C-testosterone, average valu es of duplicate incubations showed a 2.5-fold increase in DHT synthesi s in response to IGF (n = 7; P < 0.002) and a 2.3-fold increase in 4-a ndrostenedione formation (n = 7; P < 0.002). With 14C-4-androstenedion e as substrate, IGF stimulated a 2.7-fold increase in DHT synthesis (n = 5; P < 0.1) compared with controls and a 1.8-fold increase in testo sterone formation (n = 5; P < 0.1). Since both DHT and IGF are implica ted in protein turnover by fibroblasts, significant stimulation of DHT synthesis by IGF in gingiva and cultured fibroblasts is suggestive of a possible mechanism for mediating inflammatory repair via the androg en metabolic pathway.