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Effects of the anti‐androgen finasteride on 5α‐reduction of androgens in the presence of progesterone in human gingival fibroblasts: modulatory actions of the alkaline phosphatase inhibitor levamisole
Author(s) -
Tilakaratne A.,
Soory M.
Publication year - 2000
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1034/j.1600-0765.2000.035004179.x
Subject(s) - finasteride , endocrinology , medicine , dihydrotestosterone , testosterone (patch) , androgen , chemistry , androstenedione , 5 alpha reductase inhibitor , alkaline phosphatase , nandrolone , anabolism , biology , enzyme , hormone , biochemistry , prostate , cancer
Oestrogens and androgens stimulate collagen matrix synthesis, while progesterone is a competitive inhibitor for the 5α‐reduction of testosterone to 5α‐dihydrotestosterone (DHT). The anti‐androgen finasteride is a specific inhibitor of the 5α‐reductase type 2 isoenzyme, associated with anabolic functions. The aim of this investigation is to study the effects of progesterone and finasteride on 5α‐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 μg/ml, alone and in combination, for 24 h. Similarly, the effects of the alkaline phosphatase inhibitor levamisole (L, 30 μg/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 <0.01). The combination of P+F showed a similar degree of inhibition (68–78%) of DHT synthesis to that of F alone ( n =8; p <0.01). There was 35–56% stimulation of 17β‐HSD (hydroxysteroid dehydrogenase) activity by P, F and P+F ( n =8; p <0.01). When 14C‐4‐androstenedione was used as substrate there was 47% inhibition of 5α‐reductase activity at higher concentrations of P and 63 and 44% stimulation at 0.5 and 1 μg/ml ( n =8; p <0.01). F and P+F caused 40–67% inhibition of this activity. P, F and P+F caused 2–2.7‐fold stimulation of 17β‐HSD activity in response to all concentrations studied. L inhibited DHT synthesis from both substrates by 36–38%, with further inhibition of 55–70%( n =4; p <0.01), with P; this is suggestive of ligand‐independent alkaline phosphatase activity mediated by 5α‐reductase. Inhibition of 5α‐reductase activity by finasteride in gingival fibroblasts is suggestive of target tissue anabolic functions in gingivae and competitive inhibition by progesterone, is suggestive of regulation of hormone mediated tissue responses during repair.