Soory M, Tilakaratne A
Department of Periodontology, GKT Dental Institute, King's College, Caldecot Road, London, UK.
Arch Oral Biol. 2000 Apr;45(4):257-65. doi: 10.1016/s0003-9969(99)00143-0.
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.
抗菌药物米诺环素对结缔组织和骨骼具有基质刺激作用。本研究旨在探讨米诺环素对骨膜成纤维细胞中雄激素底物5α还原为5α-二氢睾酮（DHT）的影响，以及抗雄激素药物非那雄胺对这种转化的影响。从骨表面分离的口腔骨膜建立的骨膜成纤维细胞汇合培养物，在多孔培养皿中一式两份培养，加入两种雄激素底物，即[(14)C]-睾酮/[(14)C]-4-雄烯二酮，同时存在或不存在系列浓度的米诺环素或抗雄激素药物非那雄胺或两者联合使用，培养24小时。形成的代谢产物用乙酸乙酯进行溶剂萃取，通过薄层色谱法分离，并用放射性同位素扫描仪进行定量。两种雄激素底物均代谢为DHT和4-雄烯二酮或睾酮。米诺环素在20 - 30微克/毫升时，刺激这些底物合成DHT的量增加75 - 83%（n = 4；p < 0.01）。非那雄胺在1微克/毫升时抑制这些底物的5α还原酶活性3 - 5倍，在0.01和0.1微克/毫升时抑制40 - 80%（n = 4；p < 0.01），而17β-羟基类固醇脱氢酶活性变化不大。米诺环素和非那雄胺联合使用时，对一种底物表现出中间反应。由于非那雄胺抑制与合成代谢功能相关的2型5α还原酶同工酶，这些发现表明骨膜成纤维细胞在基线时以及对米诺环素反应时具有靶组织雄激素代谢活性。这对米诺环素辅助治疗期间患病牙周组织的修复潜力具有重要意义。
