The influence of prostaglandins on steroid conversions by human gingival fibroblasts

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Abstract

The aim of this investigation was to study the effects of prostaglandins E1 and E2 (PGE1 and PGE2) on the accumulation, release and metabolism of C19 steroids by human gingival fibroblasts (HGF) and gingivae, due to their anabolic potential in inflammatory repair. For the accumulation studies, HGF were incubated with 14C-testosterone at timed intervals and the cell-digests analysed for label uptake. The release of 5α-dihydrotestosterone (DHT) by HGF was studied by preincubating the cells with 14C-DHT and reincubating with cold steroid to quantify its release at timed intervals. For the metabolic studies, HGF/gingival tissue were incubated with 14C-testosterone and serial concentrations of PGE1 and PGE2 to study their effects on the synthesis of DHT. The incubations were terminated at 24 h and extracted metabolites were analysed and quantified. The accumulation of 14C-testosterone by human gingival fibroblasts was elevated 3-fold at 24 h by PGE1 (n = 3, p < 0.001; 1-way ANOVA). The release of 14C-DHT was enhanced nearly 2-fold by PGE1 (n = 3, p < 0.001), compared with controls. Both PGE1 and PGE2 caused 2-fold increases in DHT synthesis by HGF and 3-fold increases in 4-androstenedione formation (n = 4, p < 0.001). With the tissue incubations PGE1/PGE2 caused 3-4-fold increases in DHT synthesis (n = 5, p < 0.005; Wilcoxon signed rank statistic for paired observations). Direct stimulation of the accumulation/release and metabolism of these steroids by prostaglandins in gingivae may contribute to the anabolic potential of androgens in inflammatory periodontal disease.

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