Effects of the anti-androgen finasteride on the modulatory actions of oestradiol on androgen metabolism by human gingival fibroblasts.
5 alpha-Reduction of androgen substrates results in the formation of the biologically active androgen 5 alpha-dihydrotestosterone (DHT), while 17 beta-hydroxysteroid dehydrogenase metabolises androgen substrates to 4-androstenedione or testosterone. The aim here was to study the effect of the anti-androgen finasteride on 5 alpha-reduction of androgens by human gingival fibroblasts (HGF) and its modulation by oestradiol-17 beta. 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-17 beta (O) or finasteride (F; 0.1-3 microg/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 5 alpha-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.
Tilakaratne
A
A
Department of Periodontology, Faculty of Dental Sciences, University of Peradeniya, Peradeniya, Sri Lanka.
Soory
M
M
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors; D000328:Adult; D000735:Androstenedione / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology* / Q000502:physiology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D018120:Finasteride / Q000494:pharmacology*; D008401:Gas Chromatography-Mass Spectrometry; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D018709:Statistics, Nonparametric; D013739:Testosterone / Q000378:metabolism*
D058891:5-alpha Reductase Inhibitors; D004791:Enzyme Inhibitors; D013196:Dihydrotestosterone; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol; D018120:Finasteride; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase