http://www.nature.com/jid/journal/v130/n2/full/jid2009225a.html
Questo studio cambia un po' le carte in tavola
To further characterize 5#945;-Red activity, we added 1#8201;#956;m finasteride, a well known 5#945;-Red inhibitor, to the incubation medium (Figure 1c). Although finasteride is eightfold less efficient in the inhibition of type 1 compared with type 2 5alpha;-Red and is identified in the literature as a specific inhibitor of type 2 5alpha-Red (Andersson et al., 1991), we found, using human embryonic kidney (HEK)-293 cells stably expressing types 1, 2, and 3 5alpha;-Reds, that this compound inhibits these enzymes with IC50 (half maximal inhibitory concentration) values of 107, 14, and 17 nm, respectively, thus indicating that finasteride is still a relatively potent inhibitor of type 1 5alpha-Reductase.
As illustrated in Figure 1c, the levels of 5alpha-androstanedione and DHT are almost completely abolished in the presence of finasteride, with a concomitant accumulation of 4-androstanedione. The amounts of androsterone and DHT are undetectable in the presence of finasteride but in their absence are found at 12.9+1.1% of the control. Their levels in the presence and absence of finasteride are statistically different (P<0.001). The present data thus indicate that 5alpha-dione is produced by the 5alpha-reduction of 4-androstanedionedione. We have also observed reduced 3Beta-HSD activity in the presence of finasteride, an effect probably due to the inhibitory effect of finasteride on 3Beta-HSD activity. --> http://en.wikipedia.org/wiki/3-beta-HSD
The present data clearly show that the pathway of DHT biosynthesis from the DHEA precursor in SZ95 sebocytes does not always require T as an intermediate . The same pathway is also found in the prostate cancer cell line DU-145 (M. Samson et al., 2009). Interestingly, DHEA was recently shown to be the major androgen precursor in SZ95 sebocytes (Chen et al., 2009). Our findings are partially in contradiction with the traditional literature, which indicates that DHT is produced by the 5#945;-reduction of T, thus suggesting that the step catalyzed by 17Beta;-HSD precedes the step catalyzed by 5alpha-Red (DHEA -->; 4-androstanedione --> ; T -->; DHT). The pathway described in this report suggests that the step catalyzed by 5alpha-Red precedes the step catalyzed by 17Beta;-HSD (DHEA -->; 4-androstanedione -->; 5alpha-androstanedione --> DHT). Because 4-androstanedione possesses a higher affinity than T for 5alpha-Red (Andersson and Russell, 1990; Sugimoto et al., 1995), the proposed pathway corresponds better to the thermodynamic law. In addition, given that T binds to the androgen receptor efficiently and could activate the receptor without requiring its transformation to DHT, the transformation of T to DHT is not essential.
Morale della favola?
- Finasteride può bloccare la 5 alpha reduttasi 1, presente anche nel tessuto cerebrale (per non parlare della isoforma III, recentemente scoperta)
- Il DHT può essere maggiormente prodotto in alcuni citotipi dal DEHA senza passare per il testosterone, il che implica che agendo a monte del DEHA, inibendo la sua conversione in 4-androstanedione (detto nell'articolo 4-dione) si può ridurre a valle la formazione di DHT bypassando la 5 alpha riduzione.
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