The modulation of androgen metabolism by estradiol, minocycline, and indomethacin in a cell culture model.
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 (E1,3 microgram/ml) and minocycline (M25 microgram/ml) or indomethacin (I, 1 microgram/ml) alone and in combination (E1,3+11 or E1,3+M25 microgram/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 5alpha-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.
Tilakaratne
A
A
Department of Periodontology, Faculty of Dental Sciences, University of Peradeniya, Sri Lanka.
Soory
M
M
D000704:Analysis of Variance; D000728:Androgens / Q000378:metabolism*; D000735:Androstenedione / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D002849:Chromatography, Gas; D013196:Dihydrotestosterone / Q000378:metabolism; D004338:Drug Combinations; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D013058:Mass Spectrometry; D008660:Metabolism / Q000187:drug effects; D008911:Minocycline / Q000494:pharmacology* / Q000627:therapeutic use; D010518:Periodontitis / Q000188:drug therapy / Q000378:metabolism*; D010521:Periosteum / Q000166:cytology / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism
D000728:Androgens; D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D013196:Dihydrotestosterone; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol; D008911:Minocycline; D007213:Indomethacin