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Neuroactive steroids in human physiology and pathophysiology
Kubátová, Jana ; Hill, Martin (advisor) ; Fanta, Michal (referee)
The present diploma thesis is focused on the evaluation of steroid metabolome in body fluids in human pregnancy and parturition and also concentrates on the estimation of steroids in men with epilepsy (MWE) regarding the influence of epilepsy and its treatment with antiepileptic drugs (AEDs). The results obtained eventuate to the following conclusions: 1. They support the proposition about the key importance of corticoliberin for the timing of human parturition via stimulation of the steroidogenesis in the fetal zone of the fetal adrenal (FZ). Changes in steroid levels, however, much better predict the timing of parturition than the variation in corticoliberin. 2. The distribution of isoforms of placental oxidoreductases determines the excess of oxidized forms of the sex steroids and NAS in the fetus and the excess of their reduced forms in mother. This mechanism fundamentally affects the steroid bioactivity. The results indicate the role of NAS in pregnancy sustaining, their analgesic effect around parturition and their role in the pathophysiology of postpartum blues.
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The interaction of kainate subtypes of glutamate receptors with steroid compounds.
Fraňková, Denisa ; Krůšek, Jan (advisor) ; Adámek, Pavel (referee)
Kainate receptors belong to the family of glutamate receptors, which include NMDA, AMPA and δ receptors. Glutamate receptors are widely found in the brain and therefore they are very dynamically investigated, especially from view of pharmacology, because there is great potential for finding new and more specific modulators which could be used in the treatment of neurodegenerative diseases. The aim of this work was to extend the knowledge about the influence of neurosteroids on homomeric kainate receptors (GluK1, GluK2, GluK3) in which is the study of modulation by neurosteroids still at the beginning. We have investigated interactions of homomeric kainate receptors with selected neurosteroids (pregnenolone sulfate, pregnanolone sulfate, dehydroepiandrosterone, dehydroepiandrosterone sulfate) by using patch clamp method in the configuration of whole-cell recording and also by using microfluorometry. We have found out that the biggest modulating effect on homomeric kainate receptors is caused by pregnenolone sulfate, which inhibits glutamate responses of these receptors. Keywords kainate receptor, glutamate, neurosteroids, steroids, patch-clamp technique
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