title: The effect of minocycline on the metabolism of androgens by human oral periosteal fibroblasts and its inhibition by finasteride.
abstract: The antimicrobial minocycline has matrix-stimulatory effects on connective tissue and bone. The aim here was to study the effect of minocycline on 5alpha reduction of androgen substrates to 5alpha-dihydrotestosterone (DHT) in periosteal fibroblasts and the influence of the antiandrogen finasteride on this conversion. Confluent cultures of periosteal fibroblasts established from oral periosteum isolated from the bone surface were incubated in duplicate in multiwell dishes with two androgen substrates, [(14)C]-testosterone/[(14)C]-4-androstenedione, in the presence or absence of serial concentrations of minocycline or the antiandrogen finasteride or the two in combination for 24 h. The metabolites formed were solvent-extracted with ethyl acetate, separated by thin-layer chromatography and quantified using a radioisotope scanner. Both androgen substrates were metabolized to DHT and 4-androstenedione or testosterone. Minocycline stimulated the synthesis of DHT from these substrates by 75-83% at 20-30 microg/ml (n=4; p<0.01). Finasteride inhibited the 5alpha-reductase activity of these substrates by 3-5-fold at 1 microg/ml and 40-80% at 0.01 and 0.1 microg/ml (n=4; p<0.01), with little change in 17beta-hydroxysteroid dehydrogenase activity. Minocycline and finasteride in combination showed an intermediate response with one substrate. As finasteride inhibits the type 2, 5alpha-reductase isoenzyme associated with anabolic functions, these findings demonstrate target-tissue androgen metabolic activity in periosteal fibroblasts at baseline and in response to minocycline. This has implications for the reparatory potential of the diseased periodontium during adjunctive treatment with minocycline.
authors.affiliation: Department of Periodontology, GKT Dental Institute, King's College, Caldecot Road, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Soory
authors.forename: A
authors.initials: A
authors.lastname: Tilakaratne
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors; D000328:Adult; D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000378:metabolism*; D000735:Androstenedione / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D002855:Chromatography, Thin Layer; D013196:Dihydrotestosterone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D018120:Finasteride / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008911:Minocycline / Q000494:pharmacology*; D010510:Periodontal Diseases / Q000188:drug therapy; D010521:Periosteum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019275:Radiopharmaceuticals; D013739:Testosterone / Q000378:metabolism; D014945:Wound Healing
chemical_list: D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists; D000728:Androgens; D000900:Anti-Bacterial Agents; D002250:Carbon Radioisotopes; D004791:Enzyme Inhibitors; D019275:Radiopharmaceuticals; D013196:Dihydrotestosterone; D013739:Testosterone; D000735:Androstenedione; D018120:Finasteride; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D008911:Minocycline