The effect of minocycline on the metabolism of androgens by human oral periosteal fibroblasts and its inhibition by finasteride

The antimicrobial minocycline has matrix-stimulatory effects on connective tissue and bone. The aim here was to study the effect of minocycline on 5 alpha reduction of androgen substrates to 5 alpha-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, [C-14]-testosterone/[C-14]-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 mu g/ml (n = 4: p <0.01). Finasteride inhibited the 5 alpha-reductase activity of these substrates by 3-5-fold at 1 mu g/ml and 40-80% at 0.01 and 0.1 mu g/ml (n = 4; p <0.01), with little change in 17 beta-hydroxysteroid dehydrogenase activity. Minocycline and finasteride in combination showed an intermediate response with one substrate. As finasteride inhibits the type 2. 5 alpha-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. (C) 2000 Elsevier Science Ltd. All rights reserved