Could a male fertility pill adversely affect inhibition via allopregnanolone levels?
Matthew.Kirkcaldie at deletethis.newcastle.edu.au
Tue Oct 7 21:40:44 EST 2003
Just a comment - our lab works with allopregnanolone and we
pharmacologically inhibit its synthesis by administering the competetive
substrate finasteride (it outcompetes 5-alpha-dihydroprogesterone, the
natural substrate of 5-alpha-reductase, which is the final synthetic
step in making allopregnanolone).
At physiologically effective doses the finasteride is capable of
inducing seizures by upsetting the GABA-glutamate balance in the cortex.
However, you have to push the system hard to do this.
My impression is that the synthesis and activity regulation of
allopregnanolone is of sufficient potency with regard to balancing
inhibition and excitation, that it is likely to be controlled very
tightly. Although it hasn't been shown directly for allopregnanolone,
the processes of sulfation and desulfation are able to regulate
neurosteroid actions in a manner directly comparable to phosphorylation
for proteins, and I would suspect that there is a large pool of
deactivated allopregnanolone sulfate in the cell body, of which a minute
proportion is activated at any given time. In fact I presented this
hypothesis with some preliminary immunohistochemical data at the
Australian Neuroscience Society meeting in January this year (in
conjunction with Yuri Saalman who did the initial assays).
So I don't think it's of immediate concern - finasteride has been used
clinically for baldness for some time without reports of side effects,
and it's a direct blocker of allopregnanolone synthesis at high levels.
A competitor for progesterone is one synthesis step further up the chain
and hence one order of magnitude less likely to interfere with
allopregnanolone synthesis on demand, especially if the active pool is
determined by a sulfation / desulfation equilibrium.
Hope that's a useful comment.
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