| LE Magazine March 2003 |
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.
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
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