Ockham’s Razor and Selective Androgen Receptor Modulators (SARMs): Are We Overlooking the Role of 5α-Reductase?

Tissue-specific expression of 5α-reductase contributes to the tissue selectivity of SARMs. (A) Partial agonist activity of testosterone in the prostate was revealed when co-administered with type 2 5α-reductase inhibitor finasteride. Dose-response curves of T in the levator ani muscle (•) and T in the prostate (○ and dotted line) were redrawn with permission from Ostrowski et al. (12); and dose-response curves of T in the prostate with (▴) or without (▵ and dash line) co-administration of finasteride were redrawn with permission from Wright et al. (14). T data from two different studies [Wright et al. (14) dotted line; and Ostrowski et al. (12) dash line] are compared directly here, considering the fact that both studies used a re-growth model (T treatment after castration caused complete shrinkage of the prostate) with SD rats of similar age and subcutaneous administration of T. Furthermore, the dose-response curves of T in the prostate (largely DHT due to 5α-reductase action) obtained from two studies largely overlap, with similar ED₅₀ values between 0.3~0.4 mg/kg/day, showing that these two studies are comparable. (B) Partial agonist activity of SARM (hydantoin analog BMS-564929) in the prostate when administered alone. BMS-564929 was orally administered because it is orally available. Dose-response curves redrawn with permission from (12).] T, testosterone.