THE SYNTHESIS OF 5-ALPHA-DIHYDROTESTOSTERONE FROM ANDROGENS BY HUMAN GINGIVAL TISSUES AND FIBROBLASTS IN CULTURE IN RESPONSE TO TGF-BETA AND PDGF

The effects of TGF-beta and PDGF on the metabolic conversion of 14C-te stosterone by human gingival tissue (HGT) from 5 subjects was investig ated. The metabolic conversions in response to TGF-beta and PDGF were also studied in 4-6 cell-lines of cultured gingival fibroblasts, using 14C-testosterone and 14C-4-androstenedione as substrates. Duplicate i ncubations of HGT were performed in Eagle's MEM + 10% FCS and optimal stimulatory concentrations of TGF-beta/PDGF for 24 h. Similar incubati ons were performed in duplicate with cell-lines of cultured gingival f ibroblasts, TGF-beta/PDGF, 14C-testosterone/14C-4-androstenedione in E agle's MEM + 10% FCS. The radioactive metabolites were extracted, sepa rated and quantified. With HGT, TGF-beta and PDGF caused 2.5/2-fold in creases in DHT synthesis (p<0.1; Wilcoxon signed rank test) and 3.4/2- fold increases in 4-androstenedione formation (p<0.1) from 14C-testost erone. PDGF increased DHT and testosterone synthesis from 14C-4-andros tenedione by 3-fold in gingivae (p<0.1). With cell-lines, average valu es of duplicate incubations showed 2.8/2-fold increases in DHT synthes is from 14C-testosterone in response to TGF-beta/PDGF (p<0.1; p<0.2) a nd 2.4/2-fold increases in 4-androstenedione synthesis (p<0.1; p<0.2). With 14C-4-androstenedione as substrate, TGF-beta/PDGF caused 1.6/1.9 -fold increases in DHT synthesis compared with controls (p<0.05; p<0.1 ) and 1.7/1.5-fold increases in testosterone formation from this subst rate (p<0.05; p<0.1). Due to the strong implications of TGF-beta/PDGF and anabolic androgens on matrix repair, significant increases in DHT synthesis from 2 androgenic substrates in response to TGF-beta and PDG F are of particular relevance to inflammatory repair processes.