Dexamethasone-mediated androgen metabolism in human gingival and oral periosteal fibroblasts.
Dexamethasone modulates the effects of other hormones and mediates cell function; the periodontium is a target tissue for androgens. It was therefore relevant to investigate the modulation of androgen metabolism by dexamethasone in cultured human gingival (HGF) and oral periosteal fibroblasts (HPF). Each cell line was incubated in Eagle minimum essential medium with [(14)C]testosterone/[(14)C]4-androstenedione as substrates and serial concentrations of dexamethasone (0.5-50 microg/ml), for 24h; the medium was solvent-extracted, analyzed and quantified for steroid metabolites. In response to dexamethasone, both HGF (n=6) and HPF (n=4) showed up to two-fold increases in the formation of 5alpha-dihydrotestosterone and 4-androstenedione (P<0.01, one-way ANOVA), and 3.6- to 5-fold increases in the formation of testosterone (P<0.001), from [(14)C]4-androstenedione, with some inhibition at higher concentrations. Dexamethasone stimulated the formation of physiologically active androgen metabolites in a dose-dependent manner. These metabolites might therefore contribute to dichotomous effects in connective tissues of the periodontium, dependent on effective concentrations of dexamethasone.
Tilakaratne
A
A
Department of Periodontology, Faculty of Dental Science, University of Peradeniya, Peradeniya, Sri Lanka.
Soory
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M
D000328:Adult; D000704:Analysis of Variance; D000728:Androgens / Q000378:metabolism*; D000735:Androstenedione / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D002460:Cell Line; D002478:Cells, Cultured; D003238:Connective Tissue / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D013196:Dihydrotestosterone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010521:Periosteum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019275:Radiopharmaceuticals; D013739:Testosterone / Q000378:metabolism
D000728:Androgens; D000893:Anti-Inflammatory Agents; D002250:Carbon Radioisotopes; D005938:Glucocorticoids; D019275:Radiopharmaceuticals; D013196:Dihydrotestosterone; D013739:Testosterone; D000735:Androstenedione; D003907:Dexamethasone