Androgen metabolism in gingival hyperplasia induced by nifedipine and cyclosporin.

Three cases of gingival overgrowth induced by cyclosporin and/or nifedipine have been reported. Patient A was under medication with cyclosporin plus nifedipine, patient B with nifedipine only and patient C with cyclosporin only. The significance of androgen metabolism in gingival tissue with respect to hyperplastic changes has been studied by several workers. Hence, we have investigated whether gingival tissue from the above patients showed significant metabolism of the androgen, testosterone, to its biologically-active form, 5 alpha-dihydrotestosterone (5 alpha-DHT). Radical gingivectomy was carried out in all 3 cases to remove the hyperplastic tissue. The excised tissue was incubated with labelled testosterone in order to study the extent of androgen metabolism. Healthy gingivae from males and females produced 5 alpha-DHT (22.4 +/- 7.7, s.e.m., n = 8). Very significantly higher values (p less than 0.001) were recorded for patients A, B and C (1139, 542 and 994 fmol/mg, respectively). These represented increases of 51-, 24- and 44.4-fold, respectively over control values. Corresponding production of 4-androstenedione from testosterone was 28 +/- 8.3, s.e.m., n = 8, fmol/mg. In patients A, B and C, 4-androstenedione production was elevated: 85, 901 and 113 fmol/mg, respectively, representing increases of 3-, 32- and 4-fold. Even the lower values of 85 and 113 fmol/mg were very highly significant (p less than 0.001) compared with control values. Although healthy female gingival tissue does not metabolize testosterone significantly, in the presence of inflammation the extent of 5 alpha-DHT formation is comparable to that of male samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Hormonal influences on gingival tissue: relationship to periodontal disease.

It is the purpose of this review to survey the influence of corticosteroids, androgens, oestrogens and progesterone on gingival tissues and to show the relationship of such influences to periodontal disease. The clinical changes seen in plaque-induced gingivitis are accentuated by circulating levels of the above hormones via mechanisms such as partial immune suppression, increased fluid exudation, stimulation of bone resorption and stimulation of fibroblast synthetic activity. High counts of Bacteroides intermedius have been observed in users of oral contraceptives and also in the second trimester of pregnancy, in the absence of overt gingival inflammation. This is due to competition for binding between progesterone and naphthaquinone, which have a structural similarity; and the latter is an essential nutrient for the microbe. Hence high counts of Bacteroides intermedius may be a more sensitive indicator of an altered systemic hormonal condition than the usual clinical parameters. The main hormonal effect accentuates false pocketing, rather than initiating a change in attachment levels, except in cases of progressive periodontal disease associated with plaque induced inflammation and bone loss.

The use of human gingival fibroblasts in culture for studying the effects of phenytoin on testosterone metabolism.

In initial experiments, monolayer cultures of human gingival fibroblasts from healthy male and female subjects were incubated for various time intervals with [4-14C]-testosterone. This was rapidly taken up by the cells to reach 1.8 fmol/50,000 cells by 2 h. At 6, 12 and 24 h, the values were considerably lower (0.1-0.2 fmol/50,000 cells). In order to maintain a sufficient intracellular concentration of testosterone, unlabelled testosterone was incubated in the presence of [14C]-testosterone. This gave optimum yields of metabolites, which were separated by thin-layer chromatography and provisionally identified by comparison of their mobilities with those of authentic steroids. Final characterization of 5 alpha-dihydrotestosterone was achieved by combined capillary gas chromatography-mass spectrometry. The metabolites of testosterone were 5 alpha-dihydrotestosterone (5 alpha-DHT), 4-androstenedione, 5 alpha-androstanedione and 5 alpha-androstanediols, but the quantities formed varied with different cell lines. A similar pattern of metabolites was noted for minced human gingival tissue. Low concentrations of phenytoin generally increased the production of 5 alpha-DHT and 4-androstendione but there were marked variations between individual cell lines with regard to the magnitude of stimulation. Higher concentrations of phenytoin generally caused inhibition of steroid formation but the concentration required for this again varied with different cell lines. Thus human gingival fibroblasts in culture provide a suitable model for the study of testosterone metabolism and of the effects of drugs such as phenytoin. Variation in these effects may be reflected in individual susceptibility to phenytoin-induced gingival overgrowth.