Google Groups no longer supports new Usenet posts or subscriptions. Historical content remains viewable.
Dismiss
The anti-inflammatory actions of 5AR
3 views
Skip to first unread message
Kofi
Apr 14, 2012, 2:53:54 AM4/14/12
to
5a-Reduced glucocorticoids: a story of natural selection.
Nixon M, et al. Show all
Nixon M, Upreti R, Andrew R.
J Endocrinol. 2012 Feb;212(2):111-27. Epub 2011 Sep 8.
Endocrinology, Queen's Medical Research Institute, University/British
Heart Foundation Centre for Cardiovascular Science, Edinburgh EH16 4TJ,
UK
5a-Reduced glucocorticoids (GCs) are formed when one of the two isozymes
of 5a-reductase reduces the D(4-5) double bond in the A-ring of GCs.
These steroids are largely viewed inert, despite the acceptance that
other 5a-dihydro steroids, e.g. 5a-dihydrotestosterone, retain or have
increased activity at their cognate receptors. However, recent findings
suggest that 5a-reduced metabolites of corticosterone have dissociated
actions on GC receptors (GRs) in vivo and in vitro and are thus
potential candidates for safer anti-inflammatory steroids. 5a-Dihydro-
and 5a-tetrahydro-corticosterone can bind with GRs, but interest in
these compounds had been limited, since they only weakly activated
metabolic gene transcription. However, a greater understanding of the
signalling mechanisms has revealed that transactivation represents only
one mode of signalling via the GR and recently the abilities of
5a-reduced GCs to suppress inflammation have been demonstrated in vitro
and in vivo. Thus, the balance of parent GC and its 5a-reduced
metabolite may critically affect the profile of GR signalling.
5a-Reduction of GCs is up-regulated in liver in metabolic disease and
may represent a pathway that protects from both GC-induced fuel
dyshomeostasis and concomitant inflammatory insult. Therefore,
5a-reduced steroids provide hope for drug development, but may also act
as biomarkers of the inflammatory status of the liver in metabolic
disease. With these proposals in mind, careful attention must be paid to
the possible adverse metabolic effects of 5a-reductase inhibitors, drugs
that are commonly administered long term for the treatment of benign
prostatic hyperplasia.
PMID 21903862
Nixon M, et al. Show all
Nixon M, Upreti R, Andrew R.
J Endocrinol. 2012 Feb;212(2):111-27. Epub 2011 Sep 8.
Endocrinology, Queen's Medical Research Institute, University/British
Heart Foundation Centre for Cardiovascular Science, Edinburgh EH16 4TJ,
UK
5a-Reduced glucocorticoids (GCs) are formed when one of the two isozymes
of 5a-reductase reduces the D(4-5) double bond in the A-ring of GCs.
These steroids are largely viewed inert, despite the acceptance that
other 5a-dihydro steroids, e.g. 5a-dihydrotestosterone, retain or have
increased activity at their cognate receptors. However, recent findings
suggest that 5a-reduced metabolites of corticosterone have dissociated
actions on GC receptors (GRs) in vivo and in vitro and are thus
potential candidates for safer anti-inflammatory steroids. 5a-Dihydro-
and 5a-tetrahydro-corticosterone can bind with GRs, but interest in
these compounds had been limited, since they only weakly activated
metabolic gene transcription. However, a greater understanding of the
signalling mechanisms has revealed that transactivation represents only
one mode of signalling via the GR and recently the abilities of
5a-reduced GCs to suppress inflammation have been demonstrated in vitro
and in vivo. Thus, the balance of parent GC and its 5a-reduced
metabolite may critically affect the profile of GR signalling.
5a-Reduction of GCs is up-regulated in liver in metabolic disease and
may represent a pathway that protects from both GC-induced fuel
dyshomeostasis and concomitant inflammatory insult. Therefore,
5a-reduced steroids provide hope for drug development, but may also act
as biomarkers of the inflammatory status of the liver in metabolic
disease. With these proposals in mind, careful attention must be paid to
the possible adverse metabolic effects of 5a-reductase inhibitors, drugs
that are commonly administered long term for the treatment of benign
prostatic hyperplasia.
PMID 21903862
0 new messages