Androgen metabolic response to indomethacin and the alkaline phosphatase inhibitor levamisole in fibroblasts.
OBJECTIVE
The aim of this investigation is to study the effects of indomethacin (I) and the alkaline phosphatase (ALP) inhibitor levamisole (L) on androgen 5alpha-reductase expression in gingival and periosteal fibroblasts, in the context of repair in the periodontium. Chronically inflamed human gingival fibroblasts (HGF) were used to demonstrate the comparative effects of L on HGF and human oral periosteal fibroblasts (HPF).


METHODS
Monolayer cultures of six cell lines of HPF of the fifth to ninth passage were incubated in duplicate with 14C-testosterone/14C-4-androstenedione as substrates in Eagle's MEM; I was added at concentrations of 1 and 3 microg/ml in the presence or absence of the established inhibitory concentration of 30 microg/ml L and incubated for 24 h. The medium was solvent extracted for radioactive metabolites, separated by thin layer chromatography and quantified.


RESULTS
L caused 50% inhibition of 5alpha-reductase and 17beta-hydroxysteroid dehydrogenase activity in HGF. In HPF, 5alpha-reductase expression was enhanced by I with both substrates, by 65-76% (n = 6; p<0.01), inhibited by 30-50% (n = 6; p<0.01) with L and restored to control values in combination.


CONCLUSIONS
Yields of androgen metabolites may be linked to ALP activity, with implications on healing, during adjunctive treatment of inflammatory periodontal disease with I.
Division of Periodontology, Guy's King's and St Thomas' Dental Institute, King's College Dental Hospital, Caldecot Road, London, UK. mena.soory@kcl.ac.uk
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Tilakaratne
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000187:drug effects; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000187:drug effects; D058891:5-alpha Reductase Inhibitors; D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors*; D000735:Androstenedione / Q000378:metabolism*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D002460:Cell Line; D002855:Chromatography, Thin Layer; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects*; D005881:Gingiva / Q000187:drug effects*; D005891:Gingivitis / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007978:Levamisole / Q000494:pharmacology*; D010521:Periosteum / Q000187:drug effects*; D019275:Radiopharmaceuticals; D013739:Testosterone / Q000378:metabolism*
D058891:5-alpha Reductase Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002250:Carbon Radioisotopes; D004791:Enzyme Inhibitors; D019275:Radiopharmaceuticals; D007978:Levamisole; D013739:Testosterone; D000735:Androstenedione; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D000469:Alkaline Phosphatase; D007213:Indomethacin