Using the macaque model of androgenetic alopecia, we examined the effects of two antiandrogens, oral finasteride (FS) and topical RU58841 (RU), on follicular regrowth and serum levels of T and DHT. FS is known to inhibit type II reductase and to induce follicular growth in the macaque bald scalp (Rhodes et al., J.C.E.M. 79:991, 1994). RU, a potent non-steroidal androgen receptor (AR) blocker, reduces the size of hamster flank organs by topical application (Battmann et al., J. Steroid. Biochem. Molec. Biol. 48:55, 1944). FS (1mg/kg/day) and placebo, in 10 animals each, were given for 6 months. RU (5, 0.5%) and vehicle (0.5ml/kg/day) were topically applied in a total of 10 animals (4,3,3). Skin biopsies for micromorphometric analysis (folliculogram) were taken at 0 and 6 months for FS and at 0 and 4 months for RU. The populations of anagen follicles and vellus follicles enlarged to terminal size were compared to those in pre-treatment stages; anagen follicles increased an average of 88% with FS and 103% with RU (5%) and growth of vellus follicles to terminal size was 12% with FS, and 26% with RU (5%). RU (0.5%) showed a weak effect and placebos induced no effect. Hair regrowth was observed in varying degrees with both agents; RU (5%) induced the most growth after only 2 months of treatment. Plasma RU and metabolites (10-20 ng/ml) were detected in 2 cases (5%) at 3, and one at 6, months. Serum DHT decreased about 70% and T (males) increased with FS, but exhibited no significant changes with RU. Both reduced systemic production of DHT and local AR block induced regrowth of regressed follicles in the macaque bald scalp. Although FS induced a marked decrease of DHT, DHT remaining or that produced by FS-resistant reductase (Type I) still contributed to a certain degree of follicular regression. Since T and DHT share the same receptor, a locally sufficient dose of AR blocker appears to suppress T/DHT induced follicular regression more effectively than reductase inhibition.
Financed by the National Centre for Research and Development under grant No. SP/I/1/77065/10 by the strategic scientific research and experimental development program:
SYNAT - “Interdisciplinary System for Interactive Scientific and Scientific-Technical Information”.