The response of human gingival fibroblasts to interleukin-1 in their metabolic conversion of two androgenic substrates.
The effects of interleukin-1 (IL-1) on the metabolism of two androgenic substrates, testosterone and 4-androstenedione, that can be converted to the potent anabolic metabolite 5 alpha-dihydrotestosterone (DHT) were studied. Duplicate incubations of confluent gingival fibroblasts were made in Eagle's minimum essential medium + 10% fetal calf serum, with [14C]-testosterone/[14C]-androstenedione as initial substrates and optimal stimulatory concentrations of IL-1. [14C]-testosterone was converted mainly to DHT and 4-androstenedione. There was a 1.8-fold increase in DHT synthesis (n = 7; p < 0.02) and a 1.9-fold increase in 4-androstenedione in response to IL-1 (n = 7; p < 0.02) (Wilcoxon signed-rank test for non-parametric, paired observations). [14C]-4-androstenedione was mainly converted to DHT and testosterone. There was a 1.7-fold increase in DHT synthesis in response to IL-1 (n = 8; p < 0.01), and a 1.5-fold increase in testosterone formation from [14C]-4-androstenedione in the presence of IL-1, in six of the cell lines (n = 6; p < 0.05). Both testosterone and 4-androstenedione were effective substrates in forming the potent metabolite DHT in significant amounts in response to IL-1. This is significant in view of the well-documented effects of androgens on connective tissue and bone matrix, and may have implications for the healing potential of lesions in inflammatory periodontal disease.
Kasasa
S C
SC
Department of Periodontology, King's College School of Medicine and Dentistry, London, England.
Soory
M
M
D000328:Adult; D000728:Androgens / Q000378:metabolism*; D000735:Androstenedione / Q000378:metabolism; D002478:Cells, Cultured; D003238:Connective Tissue / Q000502:physiology; D013196:Dihydrotestosterone / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005891:Gingivitis / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D008297:Male; D012038:Regeneration; D018709:Statistics, Nonparametric; D013739:Testosterone / Q000378:metabolism
D000728:Androgens; D007375:Interleukin-1; D013196:Dihydrotestosterone; D013739:Testosterone; D000735:Androstenedione