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The Modulation of Androgen Metabolism by Estradiol, Minocycline, and Indomethacin in a Cell Culture Model
Author(s) -
Tilakaratne A.,
Soory M.
Publication year - 2002
Publication title -
journal of periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.036
H-Index - 156
eISSN - 1943-3670
pISSN - 0022-3492
DOI - 10.1902/jop.2002.73.6.585
Subject(s) - androstenedione , chemistry , androgen , microgram , endocrinology , testosterone (patch) , medicine , dihydrotestosterone , metabolism , cell culture , pharmacology , ethyl acetate , hormone , chromatography , biochemistry , in vitro , biology , genetics
Background: This investigation attempts to clarify the proanabolic effects of minocycline and indomethacin by studying their effects on androgen metabolism and mediation by estradiol. A cell culture model was used with androgen substrates because of the proanabolic effects of androgen metabolites. Methods: Monolayer cultures of human gingival fibroblasts (HGF) derived from 6 patients were incubated in duplicate with 14C‐ testosterone or 14C‐4‐androstenedione as substrates and optimal concentrations of estradiol (E 1,3 μg/ml) and minocycline (M 25 μg/ml) or indomethacin (I, 1 μg/ml) alone and in combination (E 1,3 +I1 or E 1,3 +M25 μg/ml); similar experiments were carried out with human oral periosteal fibroblasts (HPF), M, I, E, and the combinations. At the end of a 24‐hour incubation period in Eagle's MEM, the medium was solvent extracted with ethyl acetate and the metabolites were separated by TLC in a benzene:acetone solvent system (4:1 v/v). The separated metabolites were quantified using a radioisotope scanner. Results: Both androgens were metabolized to 5α‐dihydrotestosterone (DHT) and 4‐androstenedione (4‐A) or testosterone (T) at baseline and in response to the agents tested, by HGF and HPF. With HGF, there were significant increases in the yields of DHT and 4‐A or T in response to M, E, and M+E, resulting in 50% to 2.4‐fold increases in these metabolites over control incubations (n = 6; P <0.01). The responses to I and combinations of I+E were similar. HPF also demonstrated significant increases of 29% to 4‐fold in the yields of androgen metabolites in response to M, E, and M+E (n = 6; P <0.01). I and E similarly increased the yields of androgen metabolites, alone and in combination. Conclusions: Adjunctive periodontal treatment with minocycline or indomethacin can contribute to hormone‐modulated anabolic responses in males and females in gingival and periosteal fibroblasts derived from a chronically inflamed source. J Periodontol 2002;73:585‐590.