I've re-posted this into bionet.toxicology and Bionet.neuroscience after
initally just in the Bio.mol.P450 ng. in hope of further discussion.
In article <Elaine.Mutch-1203971605590001 at toxres.ncl.ac.uk>,
Elaine Mutch <Elaine.Mutch at ncl.ac.uk> wrote:
in reply to Christopher Hatton
>>Last night we had an intersting talk about the high level expression of
>>CYP7B in the hippocampus, however he had not really tested to see if the
>>enzyme is expressed also in such high levels only that DHEA was the
>>What was interesting was that expression levels were over 100x greater
>>in the hippocampus, compared to the liver, and this was true for rat,
>>mouse, marmoset and human (although later poor quality sample), there
>>didn't appear to be a sex difference in expression in brain unlike in
>>liver which I thought odd for a steriod hydroxylase.
>>My main questions he couldn't answer for British Patent reasons are,
>>1, Would Sodium pentobarbitone upregulate expression ? (I use this to
>>anaethetise my animals 1 week to add cannulas into hippocampus before
>> i.c.v. of my compounds) as it does many other of the CYP genes in the liver, ovary
>>etc. I presume the Barbituates will easily cross the blood brain barrier and
>>initially have a long biological half life. (30-40 hours springs to mind)
>>2, Would DHEA or Oestrogens/ Androgens change expression levels, as
>>animals get older they get a reduction in sex hormones levels in plasma,
>>ie would a reduction in levels of hormones reduce expression levels and
>>would artificially high levels of DHEA etc increase expression?
>>I ask because I'm working in the area of Neuroprotection as my PhD but I
>>did my BSc in Toxicology, my hypothosis is that the reduction in sex
>>hormone levels increases the chance of greater neuronal damage in a
>>ischaemic stroke there is a lot of evidence for this. However if you
>>are to give prophalatic compounds to keep levels of sex hormone "high" in
>>the hippocampus to these people at risk will you all induce the expression of
>>CYP's mRNA and functional proteins and CYP7B in particular, and therefore the metabolism of said
>>compound esp. if its DHEA or related.
>>BL-Institut für Neurobiologie
>>(Is life just a game where we make up the rules while we are searching
>>for something to say, or are we just simply spiralling coils of self
>>replicating DNA- Monty Python- from "The meaning of life")
>> I think you might find the paper by
>> G. Stapleton et al (1995)
> Journal of Biological Chemistry, 270(50): 29739-29745
>> of interest. It seems to answer most of your questions.
>> Hope this helps,
>> Elaine Mutch
> Environmental & Occupational Medicine
> The Medical School
> University of Newcastle upon Tyne
> NE2 4HH
Thanks Elaine, I read it and one other references and it didn't really
answer any of the above questions although there may be a possibility of
the steriod metabolites and Sodium Pentabarbitone working at the GABA-A
receptor in the hippocampus. I now understand also about there not being
a difference in the "normal" CYP/B expression levels in the hippocampus
Still waiting and another question aswell.
3, Would DHEA in someway interfere with "learning and memory" within the
brain in general and in the Hippocampus specifically ?.
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