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.