LE Magazine March 2003
DHEA
Dehydroepiandrosterone (DHEA)-youth
hormone?
Dehydroepiandrosterone (DHEA) and its
sulphated metabolite (DHEAS) are endogenous steroid hormones,
synthesized by the adrenal cortex, gonads and central nervous
system. The secretion profile changes with age and depends on
the sex. Human DHEA and DHEAS levels decline linearly and
systematically with age and suggest the potential importance
of that parameter as a biomarker of aging. The counteraction
of DHEA against atherosclerotic disease, cancer growth,
diabetes mellitus, insulin resistance, obesity and the
influence on immunological functions are observed in
researches. DHEA influences the condition of mind, cognition
functions, memory and well-being. DHEA hormonal replacement
therapy is expected to lengthen human life by the stoppage of
physiological degeneration changes and prevention of
age-related clinical disorders.
Wiad Lek 2001;54(11-12):693-704
DHEA and sport.
Dehydroepiandrosterone (DHEA), a 19-carbon steroid, is
situated along the steroid metabolic pathway. It is the most
abundant circulating hormone in the body and can be converted
to either androgens or estrogens. It is readily conjugated to
its sulphate ester DHEAS, and they are designated as DHEA(S)
here when used together. Its secretion reaches a peak in early
adulthood and thereafter decreases, until approximately age 70
years when it reaches a concentration of approximately 20%.
Many hormonal changes may take place with aging but none is as
marked as this. This "relative DHEA deficiency" resulted in
DHEA being enthusiastically labelled by some as a fountain of
youth or an antidote to aging that would prove to be the
panacea they are seeking. Its use was also taken up
enthusiastically by the athletic community and used as a
prohormone in the belief or hope that it would be converted
mainly to testosterone in the body.
Clin J Sport Med 2002
Jul;12(4):236-41
Hippocampal perfusion and
pituitary-adrenal axis in Alzheimer's disease.
The hippocampus is involved in Alzheimer's disease (AD) and
regulates the hypothalamus-pituitary-adrenal axis (HPAA).
Enhanced cortisol secretion has been reported in AD. Increased
cortisol levels affect hippocampal neuron survival and
potentiate beta-amyloid toxicity. Conversely,
dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are
believed to antagonize noxious glucocorticoid effects and
exert a neuroprotective activity. The present study was aimed
at investigating possible correlations between hippocampus
perfusion-evaluated by SPECT (Single-Photon Emission Computed
Tomography)-and HPAA function in AD. Fourteen patients with AD
and 12 healthy age-matched controls were studied by
(99m)Tc-HMPAO high-resolution brain SPECT. Plasma
adrenocorticotropin, cortisol, and DHEAS levels were
determined at 2.00, 8.00, 14.00, 20.00 h in all subjects and
their mean values were computed. Cortisol/DHEAS ratios (C/Dr)
were also calculated. Bilateral impairment of SPECT
hippocampal perfusion was observed in AD patients as compared
to controls. Mean cortisol levels were significantly increased
and DHEAS titers were lowered in patients with AD, as compared
with controls. C/Dr was also significantly higher in patients.
Using a stepwise procedure for dependent SPECT variables, the
variance of hippocampal perfusional data was accounted for by
mean basal DHEAS levels. Moreover, hippocampal SPECT data
correlated directly with mean DHEAS levels, and inversely with
C/Dr. These data show a relationship between hippocampal
perfusion and HPAA function in AD. Decreased DHEAS, rather
than enhanced cortisol levels, appears to be correlated with
changes of hippocampal perfusion in dementia.
Neuropsychobiology
2000;42(2):51-7
Dehydroepiandrosterone prevents
oxidative injury induced by transient ischemia/reperfusion in
the brain of diabetic rats.
Both chronic hyperglycemia and ischemia/reperfusion (IR)
cause an imbalance in the oxidative state of tissues.
Normoglycemic and streptozotocin (STZ)-diabetic rats were
subjected to bilateral carotid artery occlusion for 30 min
followed by reperfusion for 60 min. Rats had either been
treated with dehydroepiandrosterone (DHEA) for 7, 14, or 21
days (2 or 4 mg/day per rat) or left untreated. Oxidative
state, antioxidant balance, and membrane integrity were
evaluated in isolated synaptosomes. IR increased the levels of
reactive species and worsened the synaptic function, affecting
membrane Na/K-ATPase activity and lactate dehydrogenase
release in all rats. The oxidative imbalance was much severer
when transient IR was induced in STZ-diabetic rats. DHEA
treatment restored H2O2, hydroxyl radical, and reactive oxygen
species to close to control levels in normoglycemic rats and
significantly reduced the level of all reactive species in
STZ-diabetic rats. Moreover, DHEA treatment counteracted the
detrimental effect of IR on membrane integrity and function:
the increase of lactate dehydrogenase release and the drop in
Na/K-ATPase activity were significantly prevented in both
normoglycemic and STZ-diabetic rats. The results confirm that
DHEA, an adrenal steroid that is synthesized de novo by brain
neurons and astrocytes, possesses a multitargeted antioxidant
effect. They also show that DHEA treatment is effective in
preventing both derangement of the oxidative state and
neuronal damage induced by IR in experimental diabetes.
Diabetes 2000 Nov;49(11):1924-31
Dehydroepiandrosterone (DHEA)
stimulates neurogenesis in the hippocampus of the rat,
promotes survival of newly formed neurons and prevents
corticosterone-induced suppression.
Treating adult male rats with subcutaneous pellets of
dehydroepiandrosterone (DHEA) increased the number of newly
formed cells in the dentate gyrus of the hippocampus, and also
antagonized the suppression of corticosterone (40 mg/kg body
weight daily for 5 days). Neither pregnenolone (40 mg/kg/day),
a precursor of DHEA, nor androstenediol (40 mg/kg/day), a
major metabolite, replicated the effect of DHEA (40
mg/kg/day). Corticosterone reduced the number of cells
labelled with a marker for neurons (NeuN) following a 28-day
survival period, and this was also prevented by DHEA. DHEA by
itself increased the number of newly formed neurons, but only
if treatment was continued throughout the period of survival.
Subcutaneous DHEA pellets stimulated neurogenesis in a small
number of older rats ( approximately 12 months old). These
results show that DHEA, a steroid prominent in the blood and
cerebral environment of humans, but which decreases markedly
with age and during major depressive disorder, regulates
neurogenesis in the hippocampus and modulates the inhibitory
effect of increased corticoids on both the formation of new
neurons and their survival.
Eur J Neurosci 2002
Aug;16(3):445-53
Effect of treatment of diabetic rats
with dehydroepiandrosterone on vascular and neural
function.
Nutritional supplementation with dehydroepiandrosterone
(DHEA) may be a candidate for treating diabetes-induced
vascular and neural dysfunction. DHEA is a naturally occurring
adrenal androgen that has antioxidant properties and is
reportedly reduced in diabetes. Using a prevention protocol,
we found that dietary supplementation of
streptozotocin-induced diabetic rats with 0.1, 0.25, or 0.5%
DHEA caused a concentration-dependent prevention in the
development of motor nerve conduction velocity and endoneurial
blood flow impairment, which are decreased in diabetes. At
0.25%, DHEA significantly prevented the diabetes-induced
increase in serum thiobarbituric acid-reactive substances and
sciatic nerve conjugated diene levels. This treatment also
reduced the production of superoxide by epineurial arterioles
of the sciatic nerve. DHEA treatment (0.25%) significantly
improved vascular relaxation mediated by acetylcholine in
epineurial vessels of diabetic rats. Sciatic nerve
Na+-K+-ATPase activity and myoinositol content was also
improved by DHEA treatment, whereas sorbitol and fructose
content remained elevated. These studies suggest that DHEA, by
preventing oxidative stress and perhaps improving sciatic
nerve Na+-K+-ATPase activity, may improve vascular and neural
dysfunction in diabetes.
Am J Physiol Endocrinol Metab 2002
Nov;283(5):E1067-75
Neurosteroid quantification in human
brain regions: comparison between Alzheimer's and nondemented
patients.
Some neurosteroids have been shown to display beneficial
effects on neuroprotection in rodents. To investigate the
physiopathological significance of neurosteroids in
Alzheimer's disease (AD), we compared the concentrations of
pregnenolone, pregnenolone sulfate (PREGS),
dehydroepiandrosterone, dehydroepiandrosterone sulfate
(DHEAS), progesterone and allopregnanolone, measured by gas
chromatography-mass spectrometry, in individual brain regions
of AD patients and aged nondemented controls, including
hippocampus, amygdala, frontal cortex, striatum, hypothalamus
and cerebellum. A general trend toward decreased levels of all
steroids was observed in all AD patients' brain regions
compared with controls: PREGS and DHEAS were significantly
lower in the striatum and cerebellum, and DHEAS was also
significantly reduced in the hypothalamus. A significant
negative correlation was found between the levels of cortical
beta-amyloid peptides and those of PREGS in the striatum and
cerebellum and between the levels of phosphorylated tau
proteins and DHEAS in the hypothalamus. This study provides
reference values for steroid concentrations determined by gas
chromatography-mass spectrometry in various regions of the
aged human brain. High levels of key proteins implicated in
the formation of plaques and neurofibrillary tangles were
correlated with decreased brain levels of PREGS and DHEAS,
suggesting a possible neuroprotective role of these
neurosteroids in AD.
J Clin Endocrinol Metab 2002
Nov;87(11):5138-43
Sex hormones and their impact on
dementia and depression: a clinical perspective.
Sex hormones have often been associated with changes in
behavioral and mental abilities. This paper reviews the
scientific literature published between 1990 and 2000
investigating the effects of oestrogen, testosterone and
dehydroepiandrosterone (DHEA) on depression and dementia.
Oestrogen seems to have a positive effect in preventing, but
not treating, Alzheimer's disease. Oestrogen use may also
improve mood amongst women with postnatal or perimenopausal
depression; however, it may contribute to increasing
depressive symptoms in women with premenstrual dysphoria. The
behavioural effects of testosterone and DHEA remain unclear
but the results of preliminary reports suggest that their use
is associated with improved mood. At present, there is not
enough hard data to support the use of sex hormones and DHEA
for the treatment of depression or memory deficits.
Expert Opin Pharmacother 2001
Apr;2(4):527-35
Continued on Page 2 of 3
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