Posted by Adam on July 19, 2000, at 0:52:48
Just read (a bit late, perhaps) an interesting article in PNAS about the role of a particular neurosteroid (gets me thinking of DHEA), allopregnanolone (since done some reading elsewhere as well). In a nutshell, it is a metabolite of progesterone (via 5-alpha reductase -> dihydroprogesterone -> 3-alpha hydroxysteroid dehydrogenase -> allopregnanolone). I guess people have been interested in its relationship to mood because of its relationship to progesterone and pre-menstrual dysphoria. Since progesterone levels drop dramatically during the late stages of the regression of the corpus luteum, and this "luteal" phase is associated with PMD, progesterone (or a metabolite) was obviously implicated, though not definitively. It was also known that allopregnanolone aids in the binding of GABA to the GABA(A) receptor, thus linking it to disorders such as anxiety. The authors demonstrate that SSRIs enhance the activity of 3-alpha hydroxysteroid dehydrogenase, thus increasing the synthesis of allopregnanolone. This might explain a great deal about the efficacy of SSRIs for some anxiety disorders and PMD. I also read a blurb elsewhere about the used of an inhibitor of 5-alpha reductase, finasteride, to reduce the anticonvulsant effects of ethanol in rats, via reduction of, well, the reduction of progesterone, thus cutting off the supply of the metabolic intermediate. It was suggested this approach could be applied to alcoholism, by cutting off part of the "reward" stimulus associated with EtOH abuse: Specifically, you reduce the potential of GABA to bind a receptor by cutting off the supply of allopregnanolone, and thus remove a significantly pleasing aspect of alcohol intoxication. Fascinating stuff.
http://www.pnas.org/cgi/content/full/96/23/13512
(This is why I love jounals like PNAS and JBC: Free PDFs of their articles...if only Science, Nature, Cell, etc. would follow suit...)
What I don't see mentioned anywhere is the use of allopregnanalone itself as a treatment. Could it be administered, say in a patch, to alleviate PMD or maybe anxiety?
poster:Adam
thread:40927
URL: http://www.dr-bob.org/babble/20000717/msgs/40927.html