androstene Dotaz Zobrazit nápovědu
- MeSH
- 17-ketosteroidy metabolismus MeSH
- androgeny metabolismus MeSH
- androstendion metabolismus MeSH
- biotransformace MeSH
- estrogeny metabolismus MeSH
- formaldehyd MeSH
- lidé MeSH
- mikrozomy metabolismus MeSH
- oxidace-redukce MeSH
- placenta metabolismus MeSH
- semikarbazidy MeSH
- těhotenství MeSH
- tritium MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
The ability of androstane and androstene neurosteroids with modifications at C-17, C-5, and C-3 (compounds 1-9) to influence the functional activity of inhibitory glycine and γ-aminobutyric acid (GABA) receptors was estimated. The glycine- and GABA-induced chloride current (IGly and IGABA) were measured in isolated pyramidal neurons of the rat hippocampus and isolated rat cerebellar Purkinje cells, correspondingly, using the patch-clamp technique. Our results demonstrate that all the nine neurosteroids display similar biological activity, namely, they strongly inhibited IGly and weakly inhibited IGABA. The threshold concentration of neurosteroids inducing effects on IGly was 0.1 μM, and for effects on IGABA was 10-50 μM. Moreover, our compounds accelerated desensitization of the IGly with the IC50 values varying from 0.12 to 0.49 μM and decreased the peak amplitude with IC50 values varying from 16 to 22 μM. Interestingly, our study revealed that only compounds 4 (epiandrosterone) and 8 (dehydroepiandrosterone) were able to cause a significant change in IGABA in 10 μM concentration. Moreover, compounds 3 (testosterone), 5 (epitestosterone), 6 (dihydroandrostenedione), and 9 (etiocholanedione) did not modulate IGABA up to the concentration of 50 μM. Thus, we conclude that compounds 3, 5, 6, and 9 may be identified as selective modulators of IGly. Our results offer new avenues of investigation in the field of drug-like selective modulators of IGly.
- Publikační typ
- časopisecké články MeSH
Epimerisací 3 beta-hydroxy-16-keto-androstenu byl připraven 3 alfa-hydroxy-16-keto-androstan. Dále byl připraven za podmínek Clemmensenovy redukce z 3 beta 17 alfa-dihydroxy-16-keto-androstenu-(5) 3 beta-hydroxy-16-keto-|androsten (5) a z něho oxydací 3,16-diketoandrosten-(4)
OBJECTIVE: Dehydroepiandrosterone is a long established neuroactive steroid. Some authors documented that 7-oxygenated derivatives of this steroid may be responsive at least by part for its physiological activity. METHODS: In the ventricular cerebrospinal fluid obtained from 15 patients with hydrocephalus (8 postmenopausal women and 7 men) potentially neuroactive steroid 7-oxygenated derivatives of dehydroepiandrosterone were quantified using gas chromatography/mass spectrometry. RESULTS: Besides free dehydroepiandrosterone 7-oxygenated steroids such as 7alpha- and 7beta-hydroxy-dehydroepiandrosterone, 5-androstene-3beta,7alpha,17beta-triol and 5-androstene-3beta,7beta,17beta-triol in picomolar concentration in serum and cerebrospinal fluid were found. CONCLUSION: Dehydroepiandrosterone and its 7-oxygenated derivatives are present in ventricular cerebrospinal fluid in concentration 2 -100 times lower than in serum.
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
7-Hydroxy-metabolites of dehydroepiandrosterone (DHEA) and 3beta,17beta-androstenediol (AD) possess immunomodulatory and neuroprotective properties; therefore, the measurement of these steroids in patients with autoimmune diseases or disturbances in the CNS may be of interest. A gas chromatography-mass spectrometry (GC-MS) method for the determination of 7-hydroxy-metabolites of pregnenolone, DHEA, AD, and testosterone including the parent steroids was applied to serum samples from 12 adult men (27-66 years), 13 male adolescents (13-20 years), 5 boys (6-10 years), 15 women in the follicular phase of the menstrual cycle (22-45 years), 17 women in the luteal phase (22-45 years), and 4 girls (6-10 years). The steroids were age and sex dependent, but independent of the menstrual cycle. The ratio of the 7alpha-hydroxy-metabolites to their parent steroids were age dependent, exhibiting an increasing trend (p < 0.0001, ANOVA) from pregnenolone (5%) to AD (20%). The ratio of 7beta- to 7alpha-metabolites ranged from 0.6 to 1. These results are consistent with models suggesting 7alpha-hydroxylation of the parent steroid, conversion to a 7-oxo-steroid and finally to the 7beta-hydroxylated-metabolite. Partial correlations suggested that 7-hydroxylation might reduce the concentration of circulating androgens. Despite the three times lower concentration of AD-metabolites, their antiglucocorticoid, immunomodulatory, and neuroprotective effects may be comparable to that of DHEA based on their reported greater biological activity.
- MeSH
- androstendiol analogy a deriváty krev MeSH
- dehydroepiandrosteron antagonisté a inhibitory krev MeSH
- dítě MeSH
- dospělí MeSH
- finanční podpora výzkumu jako téma MeSH
- folikulární fáze MeSH
- hydroxylace MeSH
- lidé MeSH
- mladiství MeSH
- pregnenolon analogy a deriváty krev MeSH
- referenční hodnoty MeSH
- testosteron analogy a deriváty krev MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
