Effects of the anti-androgen finasteride on 5alpha-reductase activity in human gingival fibroblasts in response to minocycline.

Abstract

In addition to their antimicrobial properties, tetracyclines have antiinflammatory and pro-anabolic effects on the reparatory potential of connective tissue and bone. The physiologically active androgen 5alpha-dihydrotestosterone (DHT) implicated in matrix synthesis is formed in gingivae from androgen substrates. The aim of this investigation is to study the androgen metabolic response of gingivae to minocycline, in the presence or absence of the anti-androgen finasteride. Chronically inflamed gingival tissue derived from 12 subjects aged 30-50 years and passaged fibroblasts derived from this source, were used for the experiments. Duplicate incubations were performed in Eagle's MEM with 14C-testosterone/14C-4-androstenedione in the presence or absence of minocycline (5-60 microg/ml) or finasteride for 24 h. The androgen substrate 14C-testosterone was metabolised mainly to DHT and 4-androstenedione, while 14C-4-androstenedione was converted mainly to DHT and testosterone. Minocycline at 20-30 microg/ml stimulated the formation of these metabolites from both substrates by 13-25%. In the tissue incubations there were 3- and 2-fold increases in DHT and 4-androstenedione formation (n=12; p<0.01). The anti-androgen finasteride caused significant inhibition of 5alpha-reductase activity on both substrates at 0.1 & 1.0 microg/ml with total inhibition at 10 & 50 microg/ml (n=3; p<0.01). Minocycline-induced stimulation of 5alpha-reductase activity was also inhibited by finasteride (n=4; p<0.02). Since finasteride inhibition of 5alpha-reductase activity is specific for the type 2 isoenzyme associated with anabolic functions of target tissue, this enzyme activity may contribute to some of the cited anabolic tissue responses to minocycline.