Effects of the anti-androgen finasteride on the modulatory actions of oestradiol on androgen metabolism by human gingival fibroblasts

5α-Reduction of androgen substrates results in the formation of the biologically active androgen 5α-dihydrotestosterone (DHT), while 17β-hydroxysteroid dehydrogenase metabolises androgen substrates to 4-androstenedione or testosterone. The aim here was to study the effect of the anti-androgen finasteride on 5α-reduction of androgens by human gingival fibroblasts (HGF) and its modulation by oestradiol-17β. Duplicate cultures of HGF were incubated with [14C]testosterone/[14C]4-androstenedione in Eagle minimum essential medium (n=6) in the presence or absence of oestradiol-17β (O) or finasteride (F; 0.1–3 μg/ml) for 24 h. The steroid metabolites were analysed and quantified using a radioisotope scanner. With [14C]testosterone as substrate, oestradiol stimulated the formation of DHT by 63% (n=6; P<0.01). In contrast, finasteride inhibited this activity by 61% (n=6; P<0.01). The combination of O+F produced 43% less inhibition than finasteride alone (n=6; P<0.01). There were 200–300% increases in the formation of 4-androstenedione in response to O and F, being less pronounced in combination. Oestradiol stimulated the formation of DHT from [14C]4-androstenedione by 300–600% and finasteride reduced the yield of DHT by 40–64%; there was less inhibition in combination with O. There were 300–700% increases in the formation of testosterone in response to F and O alone and in combination (n=6; P<0.01). Oestradiol-induced stimulation of 5α-reductase activity on androgen substrates by HGF is suggestive of hormone modulatory mechanisms in the healing periodontium of both sexes. Its inhibition by finasteride is suggestive of type 2 isoenzyme activity, confirming target-tissue functions in the gingiva.