Dehydroepiandrosterone (DHEA) and its sulfate bound form (DHEAS) are important steroids of mainly adrenal origin. They are produced also in gonads and in the brain. Dehydroepiandrosterone easily crosses the brain-blood barrier and in part is also produced locally in the brain tissue. In the brain, DHEA exerts its effects after conversion to either testosterone and dihydrotestosterone or estradiol via androgen and estrogen receptors present in the most parts of the human brain, through mainly non-genomic mechanisms, or eventually indirectly via the effects of its metabolites formed locally in the brain. As a neuroactive hormone, DHEA in co-operation with other hormones and transmitters significantly affects some aspects of human mood, and modifies some features of human emotions and behavior. It has been reported that its administration can increase feelings of well-being and is useful in ameliorating atypical depressive disorders. It has neuroprotective and antiglucocorticoid activity and modifies immune reactions, and some authors have also reported its role in degenerative brain diseases. Here we present a short overview of the possible actions of dehydroepiandrosterone and its sulfate in the brain, calling attention to various mechanisms of their action as neurosteroids and to prospects for the knowledge of their role in brain disorders.
- MeSH
- androgeny metabolismus MeSH
- centrální nervový systém embryologie MeSH
- dehydroepiandrosteron analogy a deriváty metabolismus MeSH
- dehydroepiandrosteronsulfát metabolismus MeSH
- dihydrotestosteron metabolismus MeSH
- gonády metabolismus MeSH
- kyslík metabolismus MeSH
- lidé MeSH
- mozek metabolismus MeSH
- nadledviny metabolismus MeSH
- steroidy metabolismus MeSH
- testosteron metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
In order to study a possible effect of mini-invasive heart intervention on a response of hypothalamo-pituitary-adrenal stress axis, we analyzed four stress markers (cortisol, cortisone, DHEA and DHEAS) in 25 sows using minimally invasive heart catheterisation as the stress factor. The marker levels were assessed in four periods of the experiment, (1) the baseline level on the day before intervention, (2) after the introduction of anesthesia, (3) after conducting tissue stimulation or ablation, and (4) after the end of the catheterisation. For statistical analyses we used the non-parametric Friedman test for four dependent samples (including all four stages of the operation) or three dependent samples (influence of operation only, baseline level was excluded). Statistically significant differences in both Friedman tests were found for cortisol and for cortisone. Significant differences for DHEA as well as for DHEAS were found for all tested stages but not for the effect of operation itself. We have concluded that cortisol levels are blunted by the influence of anesthesia after its administration, and therefore decrease back to the baseline at the end of the operation. The other markers (cortisone, DHEA and DHEAS) acted as balanced systems against the injurious stress effect.
- MeSH
- adrenokortikotropní hormon metabolismus MeSH
- anestezie MeSH
- dehydroepiandrosteron metabolismus MeSH
- dehydroepiandrosteronsulfát metabolismus MeSH
- hormony metabolismus MeSH
- hydrokortison metabolismus MeSH
- kortison metabolismus MeSH
- prasata MeSH
- psychický stres metabolismus MeSH
- srdeční katetrizace škodlivé účinky MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The aim of the present research was to study the uptake of DHEAS, and to establish the intracrine capacity of human platelets to produce sex steroid hormones. The DHEAS transport was evaluated through the uptake of [(3)H]-DHEAS in the presence or absence of different substrates through the organic anion transporting polypeptide (OATP) family. The activity of sulfatase enzyme was evaluated, and the metabolism of DHEAS was measured by the conversion of [(3)H]-DHEAS to [(3)H]-androstenedione, [(3)H]-testosterone, [(3)H]-estrone and [(3)H]-17beta-estradiol. Results indicated the existence in the plasma membrane of an OATP with high affinity for DHEAS and estrone sulphate (E(1)S). The platelets showed the capacity to convert DHEAS to active DHEA by the steroid-sulfatase activity. The cells resulted to be a potential site for androgens production, since they have the capacity to produce androstenedione and testosterone; in addition, they reduced [(3)H]-estrone to [(3)H]-17beta-estradiol. This is the first demonstration that human platelets are able to import DHEAS and E(1)S using the OATP family and to convert DHEAS to active DHEA, and to transform E(1)S to 17beta-estradiol.
- MeSH
- androgeny metabolismus MeSH
- androstendion metabolismus MeSH
- dehydroepiandrosteron metabolismus MeSH
- dehydroepiandrosteronsulfát metabolismus MeSH
- estradiol metabolismus MeSH
- estron analogy a deriváty metabolismus MeSH
- lidé MeSH
- přenašeče organických aniontů metabolismus MeSH
- testosteron metabolismus MeSH
- trombocyty chemie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
7-hydroxy/oxo derivatives of dehydroepiandrosterone are potential regulators of the local cortisol activity due to their competition in the cortisolcortisone balance mediated by 11ß-hydroxysteroid dehydrogenase. 7-hydroxydehydroepiandrosterone is marketed as anti-obesity medication, though no clinical study aimed at the benefit of administering 7-oxygenated derivatives of dehydroepiandrosterone has appeared until now. We tried to show whether there exist differences in levels of circulating 7-hydroxy/oxo-dehydroepiandrosterone derivatives between lean and obese boys and girls. From a cohort of adolescents investigated within the frame of anti-obesity programme 10 obese boys and 10 obese girls were compared with age-matched lean boys and girls in their anthropometric data, and concentrations of both epimers of 7-hydroxydehydroepiandrosterone and 7-oxo-dehydroepiandrosterone were determined by the RIA method. The basal levels of 7α-hydroxy-dehydroepiandrosterone were significantly higher in obese boys than in lean boys but not in girls. The association was found for anthropometric parameters and 7α-hydroxy-dehydroepiandrosterone, however again only in boys and not in girls. Higher levels of 7α-hydroxydehydroepiandrosterone its positive association with anthropometric data in obese boys may serve as a sign that, at least in boys, 7-oxygenated 5-ene-steroids may take part in regulating the hormonal signal for fat formation or distribution.
- MeSH
- adipozita MeSH
- antropometrie metody MeSH
- dehydroepiandrosteron analogy a deriváty izolace a purifikace metabolismus MeSH
- epidemiologické studie MeSH
- financování organizované MeSH
- index tělesné hmotnosti MeSH
- lidé MeSH
- mladiství MeSH
- obezita metabolismus MeSH
- statistika jako téma MeSH
- steroidy izolace a purifikace metabolismus MeSH
- tělesné váhy a míry MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
Řada laboratorních ukazatelů se liší u zdravých osob a u nemocných schizofrenií. 07em práce bylo pokusit se o odlišení nemocných se schizofrenií od zdravých osob netrpících touto chorobou na základě vybraných biochemických vyšetření, včetně neuroaktivních steroidů. Materiál a metodika: U 21 dosud neléčených (first episode) nemocných schizofrenií podle DSM-IV (13 mužů a 8 žen) a u 22 zdravých mužů a 25 zdravých žen stejného věku bylo stanoveno 16 vybraných biochemických ukazatelů zahrnujících lipidové spektrum, ukazatele tyroidální funkce, vybrané aminothioly, glykémii, prolaktin a následně 43 steroidů tvořících steroidní metabolom. Výsledky: Biochemická vyšetření potvrdila zhoršení lipidového spektra, zvýšenou homocysteinémii, prolaktinémii a poruchy tyroidální funkce u nemocných osob. Stanovení steroidního metabolomu s využitím statistické metody multivariační regrese s redukcí dimensionality umožnilo odlišit schizofrenii od zdravých osob s vysokou specificitou. Závěr: Výsledky přinesly další argument pro přítomnost autoimunitní složky v patofyziologii schizofrenie. Stanovení steroidního metabolomu se ukázalo jako možná cesta pro diagnostiku schizofrenie na základě laboratorních dat.
Many laboratory parameters differ between patients with schizophrenia and healthy subjects. The aim was to differentiate patients from healthy subjects using selected biochemical data, including levels of neuroactive steroids. Materials and methods: 16 selected biochemical parameters including lipid spectrum, parameters of thyroid function, glycaemia, pro- lactin, selected aminothiols and 43 steroids constituting steroid metabolome were measured in 21 first-episode patients with DS M-IV schizophrenia (13 males and 8 women) and in 22 age-matched healthy men and 25 women. Results: Biochemical analyses confirmed impaired lipid spectrum, increased homocysteinemia, prolactinemia and thyroid function disorders in patients. Determination of steroid metabolome using the multivariate regression method with reduction of dimensionality enabled us to differentiate schizophrenia patients from healthy subjects with a high specificity Conclusion: The results brought additional argument for autoimmunity involvement in pathophysiology of schizophrenia. Determi- nation of steroid metabolome is a potentially useful laboratory tool in diagnostics of schizophrenia.
- Klíčová slova
- steroidní metabolom, biochemická vyšetření,
- MeSH
- biologické markery analýza MeSH
- časná diagnóza MeSH
- dehydroepiandrosteron diagnostické užití metabolismus MeSH
- dlouhodobě působící stimulátor tyreoidey analýza metabolismus MeSH
- financování organizované MeSH
- lidé MeSH
- schizofrenie imunologie patofyziologie MeSH
- steroidy diagnostické užití metabolismus MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
OBJECTIVE: Mood changes occur often in the luteal phase of menstrual cycle. Steroids modulating GABAA and NAMD receptors in the brain, namely allopregnanolone, were suggested as a factor of premenstrual syndrome. Another neurosteroid influencing the well-being is dehydroepiandrosterone. In the past decade it was shown by several authors that some dehydroepiandrosterone derivatives, especially those with 7-hydroxy- or 7-oxo group, exert a higher activity than dehydroepiandrosterone itself. It was also reasonable to see whether the levels of circulating 7-hydroxy-derivatives of dehydroepiandrosterone differ in the follicular and luteal phase of the menstrual cycle. METHODS: Steroids known to exert neuroprotective effects, namely 7α- and 7β-hydroxy-dehydroepiandrosterone, 5-androstene-3β,7α,17β-triol and 5-androstene-3β,7β,17β-triol, were determined in midfollicular and midluteal phase of the menstrual cycle of 22 healthy women with a regular menstruation cycle. RESULTS: Whereas the maternal steroids, dehydroepiandrosterone and androstene-3β,17β-diol showed no significant difference between the phases of menstrual cycle, the levels of their 7-hydroxylated metabolites were significantly lower in the luteal phase. CONCLUSION: It is suggested that the observed decrease of 7-hydroxylated metabolites during the luteal phase may be a factor related to the etiopathogenesis of mood change and neurocognitive disturbances, which are known to be more accented in that particular phase of the menstrual cycle.
- MeSH
- afekt fyziologie MeSH
- dehydroepiandrosteron analogy a deriváty metabolismus MeSH
- dospělí MeSH
- folikulární fáze krev fyziologie psychologie MeSH
- hydroxylace MeSH
- lidé MeSH
- lineární modely MeSH
- luteální fáze krev metabolismus psychologie MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- cirkadiánní poruchy endokrinního systému,
- MeSH
- cirkadiánní rytmus * fyziologie genetika imunologie MeSH
- dehydroepiandrosteron fyziologie metabolismus MeSH
- depresivní poruchy enzymologie etiologie komplikace MeSH
- endokrinní systém * abnormality enzymologie patofyziologie MeSH
- estradiol izolace a purifikace metabolismus MeSH
- financování organizované MeSH
- hormony izolace a purifikace metabolismus MeSH
- hydrokortison fyziologie metabolismus MeSH
- krevní oběh - doba MeSH
- krevní tlak fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- melatonin fyziologie izolace a purifikace metabolismus MeSH
- selen metabolismus MeSH
- statistika jako téma MeSH
- testosteron fyziologie izolace a purifikace metabolismus MeSH
- únava enzymologie etiologie komplikace MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Though pathobiochemical and neurochemical changes and accompanied morphological alterations in Alzheimer dementia are well known, the triggering mechanisms, if any, remain obscure. Important factors influencing the development and progression of Alzheimer disease include hormonal steroids and their metabolites, some of which may serve as therapeutic agents. This review focusses on major biochemical alterations in the brain of Alzheimer patients with respect to the involvement of steroids. It includes their role in impairment of fuel supply and in brain glycoregulation, with especial emphasis on glucocorticoids and their counter-regulatory steroids as dehydroepiandrosterone and its metabolites. Further, the role of steroids in beta-amyloid pathology is reviewed including alterations in tau-protein(s) phosphorylation. The (auto)immune theory of Alzheimer dementia is briefly outlined, pointing to the possible involvement of steroids in brain ageing, immunosenescence and neuronal apoptosis. Some effects of steroids are briefly mentioned on the formation and removal of reactive oxygen species and their effect on calcium flux and cytotoxicity. The recent biochemical research of Alzheimer disease focusses on molecular signalling at which steroids also take part. New findings may be anticipated when the mosaic describing the molecular mechanisms behind these events becomes more complete.
- MeSH
- Alzheimerova nemoc imunologie patologie patofyziologie MeSH
- amyloidní beta-protein metabolismus MeSH
- apoptóza MeSH
- autoimunita MeSH
- dehydroepiandrosteron metabolismus fyziologie MeSH
- glukokortikoidy fyziologie terapeutické užití MeSH
- glykosylace MeSH
- lidé MeSH
- mozek metabolismus patologie MeSH
- neuroimunomodulace účinky léků MeSH
- proteiny tau metabolismus MeSH
- steroidy metabolismus fyziologie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
OBJECTIVE: Polychlorinated biphenyls (PCBs) and related compounds elicit a diverse spectrum of toxic responses. Additionally, they are able to pass through the human placenta. The aim of the presented data was to compare the action of low-chlorinated (Delor 103) and (Delor 106) high-chlorinated biphenyls on placental steroidogenesis. METHODS: Explants of human placental tissue were used to test differences in PCBs accumulation and influence on placental steroidogenesis. Delor 103 or 106, were added daily for six days at a dose of 200 pg from day 0 to day 6 of culture. The media in the control and experimental groups were changed every day, and collected and frozen for steroid analysis by RIA. Determinations of PCBs of tissue and medium were analysed by GC/MS/MS. RESULTS: Delor 103 was found at a higher level in the tissue than Delor 106. The first day of exposure to Delor 103 had no effect on the conversion of dehydroepiandrosterone (DHEA) to estradiol (E2) while there was a 2-fold decrease in E2 secretion from days 3 to 6. Conversely, Delor 106 caused an immediate increase in E2 secretion, which was maintained at higher levels throughout the exposure period. CONCLUSION: Differences between the accumulation of lower chlorinated and higher chlorinated biphenyls in human placental tissue and in the properties of the congeners can have multiple effects that may intensify or counteract the effects on uterine contraction by PCBs.
- MeSH
- aromatasa metabolismus MeSH
- dehydroepiandrosteron metabolismus MeSH
- estradiol metabolismus MeSH
- financování organizované MeSH
- látky znečišťující životní prostředí farmakokinetika farmakologie MeSH
- lidé MeSH
- placenta metabolismus účinky léků MeSH
- polychlorované bifenyly farmakokinetika farmakologie MeSH
- techniky in vitro MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
