The influence of insulin-like growth factor (IGF) on C19 steroid conversions by human gingiva and in cultured gingival fibroblasts.

Abstract

The metabolic conversion of 14C-testosterone by human gingival tissue in response to IGF was studied. Androgen metabolic studies were also performed in 5 to 7 cell-lines of cultured gingival fibroblasts, using 14C-testosterone and 14C-4-androstenedione as initial substrates. Duplicate incubations of gingival tissue were performed after establishing the wet weight, in Eagle's MEM + 10% FCS and optimal stimulatory concentrations 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 period, the radioactive metabolites were extracted, evaporated, subjected to thin layer chromatography for their separation, and quantified by scanning in a Berthold's linear analyzer. With the gingival tissue samples, IGF caused a 4-fold increase in 5 alpha-dihydrotestosterone (DHT) synthesis (n = 5; P < 0.1, Wilcoxon signed rank test for paired observations) and a 3.5-fold increase in 4-androstenedione formation (n = 5; P < 0.1) from 14C-testosterone. When similar incubations were performed with cell-lines of fibroblasts and 14C-testosterone, average values of duplicate incubations showed a 2.5-fold increase in DHT synthesis in response to IGF (n = 7; P < 0.002) and a 2.3-fold increase in 4-androstenedione formation (n = 7; P < 0.002). With 14C-4-androstenedione 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 testosterone formation (n = 5; P < 0.1). Since both DHT and IGF are implicated 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 androgen metabolic pathway.