The effect of interleukin-1 (IL-1) on androgen metabolism in human gingival tissue (HGT) and periodontal ligament (PDL).
Due to the potent anabolic effects of the androgenic metabolite 5 alpha- dihydrotestosterone (DHT) on matrix synthesis by connective tissue and bone, it was pertinent to investigate the effects of interleukin-1 (IL-1) on androgen metabolism by chronically inflamed human gingival tissue (HGT) and periodontal ligament (PDL). Duplicate incubations of HGT and PDL derived from 6 subjects (age- and sex-matched) were performed in Eagle's MEM+FCS with 14C-testosterone to study baseline conversion to DHT and 4-androstenedione. Similarly further incubations were performed for 24 h in a 5% CO2 in air incubator, with HGT and PDL from 4 comparable patients to study the effect of IL-1 on this conversion. The medium was extracted radioactive metabolites separated by thin-layer chromatography and quantified. When baseline metabolism of HGT was compared with that of PDL, both tissues metabolised 14C-testosterone to DHT and 4-androstenedione. There was a 2.4-fold increase in DHT synthesis by PDL over that of HGT (n = 6; p < 0.005) and a 2.5-fold increase in 4-androstenedione formation by PDL compared with HGT (n = 6; p < 0.01). In response to IL-1, HGT demonstrated a 2-fold increase in DHT synthesis (n = 4; p < 0.005) and a 3.5-fold increase in 4-androstenedione formation (p < 0.01) over control gingival tissue; PDL showed a 9-fold increase in DHT synthesis in response to IL-1 (n = 4; p < 0.005) and a 6-fold increase in 4-androstenedione formation (p < 0.005) over control ligament tissue. The increased androgen metabolic capacity of PDL over HGT, both at baseline and in response to IL-1 is in keeping with protein studies and may be relevant to repair processes during inflammatory periodontal disease.
Kasasa
S C
SC
Department of Periodontology, King's College School of Medicine & Dentistry, London, UK.
Soory
M
M
D000328:Adult; D000735:Androstenedione / Q000378:metabolism; D001857:Bone Matrix / Q000187:drug effects / Q000378:metabolism; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D002855:Chromatography, Thin Layer; D003238:Connective Tissue / Q000187:drug effects / Q000378:metabolism; D046508:Culture Techniques; D013196:Dihydrotestosterone / Q000378:metabolism*; D005260:Female; D005881:Gingiva / Q000187:drug effects* / Q000378:metabolism; D005891:Gingivitis / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010513:Periodontal Ligament / Q000187:drug effects* / Q000378:metabolism; D010518:Periodontitis / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism*; D014945:Wound Healing
D002250:Carbon Radioisotopes; D007375:Interleukin-1; D013196:Dihydrotestosterone; D013739:Testosterone; D000735:Androstenedione