Finasteride inhibits as well 5arI and 3beta hsd

xptriado · May 25, 2018, 7:48am

nature.com/jid/journal/v130/ … 9225a.html

To further characterize 5α-Red activity, we added 1 μm finasteride, a well known 5α-Red inhibitor, to the incubation medium (Figure 1c). Although finasteride is eightfold less efficient in the inhibition of type 1 compared with type 2 5α-Red and is identified in the literature as a specific inhibitor of type 2 5α-Red (Andersson et al., 1991), we found, using human embryonic kidney (HEK)-293 cells stably expressing types 1, 2, and 3 5α-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 5α-Red. Moreover, finasteride inhibited type 1 5α-Red in higher concentrations in SZ95 sebocytes (Seiffert et al., 2007). As illustrated in Figure 1c, the levels of 5α-dione and DHT are almost completely abolished in the presence of finasteride, with a concomitant accumulation of 4-dione. 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 5α-dione is produced by the 5α-reduction of 4-dione. We have also observed reduced 3β-HSD activity in the presence of finasteride, an effect probably due to the inhibitory effect of finasteride on 3β-HSD activity. Indeed, we have previously shown that 4-MA (N,N-dimethyl-4-methyl-3-oxo-4-aza-5α-androstane-17β-carboxamide), a potent inhibitor of 5α-Red that has a structure somewhat similar to that of finasteride, is also a potent inhibitor of 3β-HSD activity (Takahashi et al., 1990; Luu-The et al., 1991).

xptriado · May 25, 2018, 7:48am

Jsut throwing in some more ashes!

I wish the people who released this medication as a hairloss treatment rotten to death!

xptriado · May 25, 2018, 7:48am

The fact its ic50 for inhibition of 5ar I is lower inside sebacytes, could prob account for the dry skin people experience and for a part of the low dht.

Whats your opinion?

Costa · May 25, 2018, 7:48am

whatever fin inhibits, it ceases to do so after discontinuation. The problem might not lie there, but on how does the body react to such inhibitions. Does it alter gene expression in order to correlate? Does it apply changes on the receptors? Who knows…

xptriado · May 25, 2018, 7:48am

What are you proposing then? That we dont need to understand how it works?

Of course we have to know where the drug acted in the first place to better understand what has happened uppn discontinuation!

Costa · May 25, 2018, 7:48am

I thought we already knew that.

xptriado · May 25, 2018, 7:48am

What did we already know…

depressedguy · May 25, 2018, 7:48am

i guess he is talking abot neurosteroids??
or androgen receptors?