Effect of streptozotocin-induced diabetes on the gene expression and biological activity of 3 beta-hydroxysteroid dehydrogenase in the rat spinal cord
Articolo
Data di Pubblicazione:
2005
Citazione:
Effect of streptozotocin-induced diabetes on the gene expression and biological activity of 3 beta-hydroxysteroid dehydrogenase in the rat spinal cord / S. Saredi, C. Patte-Mensah, C. Melcangi, A.G. Mensah-Nyagan. - In: NEUROSCIENCE. - ISSN 0306-4522. - 135:3(2005), pp. 869-877.
Abstract:
Abnormal secretion of steroids by the adrenals
and gonads is one of the disturbances occurring in diabetics
but the impact of diabetes on steroid formation in the nervous
system has never been studied. However, it is well
known that numerous actions of peripheral steroids on the
nervous system require their conversion into neuroactive
metabolites within the neural tissue. As this in situ steroid
synthesis/metabolism is crucial for the control of several
neurobiological functions, we investigated the effects of
streptozotocin-induced diabetes on the gene expression and
activity of 3 -hydroxysteroid dehydrogenase in the spinal
cord, a pivotal structure involved in sensorimotor and neurovegetative
mechanisms. 3 -Hydroxysteroid dehydrogenase
is a key enzyme which participates to the biosynthesis
of all classes of steroids by converting 5-3 -hydroxysteroids
such as pregnenolone and dehydroepiandrosterone
into 4-3-ketosteroids as progesterone and androstenedione,
respectively. Reverse transcription coupled with quantitative
real-time polymerase chain reaction revealed that 3 -hydroxysteroid
dehydrogenase gene was over-expressed in the spinal
cord of streptozotocin-treated rats compared with controls.
Pulse-chase experiments combined with high performance
liquid chromatography and continuous flow detection
of newly-synthesized steroids showed an increase of 3 -
hydroxysteroid dehydrogenase activity responsible for a hyper-
production of progesterone in the spinal cord of diabetic
rats. This up-regulation of progesterone biosynthesis was
concomitant with a decrease of its transformation into tetrahydroprogesterone,
a process which facilitated progesterone
accumulation in the spinal cord of streptozotocin-treated
rats. Since progesterone is a potent neuroprotective steroid,
increase of its production appeared as an endogenous molecular
and biochemical mechanism triggered by spinal nerve
cells to cope with degenerative effects of streptozotocininduced
diabetes. Our results constitute the first direct evidence
showing an impact of diabetes on steroid biosynthetic
and metabolic pathways in the nervous system. The data
open new perspectives for the modulation of deleterious
effects of diabetes by neuroprotective steroids.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Diabetes; Neuroprotection; Neurosteroid; Real-time PCR; Spinal cord; Steroids and the nervous system
Elenco autori:
S. Saredi, C. Patte-Mensah, C. Melcangi, A.G. Mensah-Nyagan
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