Effects of the anti-androgen finasteride on 5 alpha-reduction of androgens in the presence of progesterone in human gingival fibroblasts: modulatory actions of the alkaline phosphatase inhibitor levamisole

Oestrogens and androgens stimulate collagen matrix synthesis, while progesterone is a competitive inhibitor for the 5 alpha-reduction of testosterone to 5 alpha-dihydrotestosterone (DHT). The anti-androgen finasteride is a specific inhibitor of the 5 alpha-reductase type 2 isoenzyme, associated with anabolic functions. The aim of this investigation is to study the effects of progesterone and finasteride on 5 alpha-reduction of androgen substrates by human gingival fibroblasts. Monolayer cultures of human gingival fibroblasts (HGF) of the 4th-9th passage were established in Eagle's minimum essential medium (MEM). Duplicate incubations were performed with 14C-testosterone/14C-4-androstenedione as substrates and progesterone (P) or finasteride (F), at concentrations of 0.5, 1, 3 and 5 mu g/ml, alone and in combination, for 24 h. Similarly, the effects of the alkaline phosphatase inhibitor levamisole (L, 30 mu g/ml) and P were studied. Steroid metabolites were analysed and quantified, using a radioisotope scanner. Progesterone inhibited DHT synthesis in HGF from 14C-testosterone by 24-62% (n = 8; p <0.01). Finasteride caused 59-82% inhibition (n=8;p