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Effect of stress on expression of 11β-hydroxysteroid dehydrogenase in rat brain
Kuželová, Andrea ; Pácha, Jiří (advisor) ; Vybíral, Stanislav (referee)
This thesis examines the influence of stress on the activity of hippocampal CA1 area. The main task was to determine whether the stress load affects the changes of the local metabolism of glucocorticoids, and whether the levels of corticosteroid receptors in the CA1 hippocampus are modulated in response to stress. In order to answer these questions, the experiments were carried out using three different rat strains - Fisher, Lewis and Wistar which differ in their activities of hypothalamic-pituitary-adrenal axis. Our results demonstrate that stress has no effect on expression of MR mRNA. Conversely, stress reduces the levels of GR mRNA in CA1 area of the dorsal hippocampus. Moreover, we confirmed that the Lewis and Wistar rats didn't change metabolism of glucocorticoids after stress response. By the Fisher rats increased levels of 11β-HSD1 mRNA expression and therefore increased the metabolism of corticosterone.
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Effect of stress on corticosteroid metabolism in peripheral tissues
Makal, Jakub ; Pácha, Jiří (advisor) ; Vybíral, Stanislav (referee)
Stressor influence can lead to homeostatic disruption. To eliminate this threat, mechanism which compensates negative effects of stressor was evolved by organisms. It's called stress response. One of two major systems that moderate stress response of organism is hypothalamic- pituitary-adrenal axis (HPA axis). Effectors of the HPA axis are glucocorticoids, steroid hormones secreted from adrenal glands. Enzymes which metabolize glucocorticoids are located in target tissues for these hormones. They convert active glucocorticoids into their inactive forms, or vice versa. Untill now, two such enzymes have been described - 11beta-hydroxysteroid dehydrogenases type 1 and type 2. It was proved that expression and activity of these enzymes can change under the influence of stressor. These changes are tissue-specific and dependent on type of applied stressor.
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Noninvasive measurement of steroid homones and effect of hormonal manipulation on behaviour in the gecko Paroedura picta
Matušková, Lucie ; Kratochvíl, Lukáš (advisor) ; Fraňková, Marcela (referee)
Hormones influence life of all animals. Not only they affect physiological changes in organisms, but also impact their behaviour. This work focuses at two main groups of steroid hormones: glucocorticoids and androgens. Glucocortiods are activated in response to stress. Their levels can be measured using non-invasive methods, which have a range of advantages. The main advantage is the feedback-free sample collection for enzyme immunoassay. As the measurement involves metabolites of the hormones rather than the hormones themselves, prior validation of the method is, however, necessary. This work reports on a study aiming to validate non-invasive measurement on the Madagascar Ground Gecko (Paroedura Picta). The validation was based on ACTH challenge test: Synacthen Depot was injected, which should lead to increased blood level of glucocorticoids. The validation, however, was not successful. The measurement did not discover significant increase in the levels of the metabolites of glucocorticoids. In addition, the work focuses on behavioural effects of testosterone, the primary androgen. Hormonal manipulations have been carried out on several male and female specimens. The results have discovered differences in sexual behaviour between control groups. On the other hand, the hormonal manipulations had no...
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Endogenous steroid dehydroepiandrosterone and its role in modulation of local metabolism of glucocorticoids
Imrichová, Terezie ; Pácha, Jiří (advisor) ; Kůs, Vladimír (referee)
The anti-glucocorticoid effect of dehydroepiandrosterone (DHEA) have been known for many years. However, its molecular basis have not been elucidated yet. The results of certain experiments suggest that not DHEA but its 7-oxygenated metabolites 7-OH-DHEA, 7-OH-DHEA a 7-oxo-DHEA are the antiglucocorticoid molecules. Various hypothesis about how these steroids exert their antiglucocorticoid action have been tested during the last several years. Some of them were reliably disproved (e.g. the competitive inhibition of glucocorticoid receptors), others were validated (e.g. the DHEA-mediated change in expression of certain enzymes participating in glucocorticoid metabolism), and yet others are still being considered. Nevertheless, clarifying the nature of the anti-glucocorticoid effect of DHEA or its metabolites is crucial for its possible use as a therapeutic drug.
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Bacterial components in experimental intestinal inflammation prevention and therapy
Kverka, Miloslav ; Tlaskalová - Hogenová, Helena (advisor) ; Šedivá, Anna (referee) ; Stříž, Ilja (referee)
Although strong protective immune response is essential for preventing invasion by pathogens, equivalent responses against antigens originating from commensal bacteria can lead to chronic inflammatory diseases, such as inflammatory bowel disease (IBD). Manipulating the mucosal immune responses with microbial antigens might be an excellent tool to IBD therapy or prevention. Our aim was to gain some insight into the regulation of the intestinal inflammation and to isolate bacterial immunomodulatory components that could be used in intestinal inflammation therapy and prevention. One particular mechanism of how healthy colon tissue regulates the inflammation during acute experimental colitis is through modulation of bioavailability of glucocorticoids (GCs) in gut mucosa. Here, we show that intestinal inflammation changes the local GC metabolism, which ultimately leads to decrease in inflammatory readiness of cells in the gut mucosa and in mesenteric lymph nodes. This pre-receptor regulation of GC function could represent an important homeostatic function of the gut mucosa. The actual triggers of intestinal inflammation in IBD seem to be either microbial dysbiosis or microbes with special "pathogenic" abilities, which both could be rectified by feeding with probiotics. Here, we report that oral feeding with live...
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Local metabolism of glucocorticoids in female Prague hereditary hypertriglyceridemic rats
Klusoňová, Petra ; Pácha, Jiří (advisor) ; Kopecký, Jan (referee) ; Haluzík, Martin (referee)
11-hydroxysteroid dehydrogenase (11HSD1) is an oxidoreductase which catalyzes conversion of inactive 11-oxo steroid derivatives into active 11-hydroxy forms. 11HSD1 elevates intracellular level of active glucocorticoid (GC) hormones: cortisol in human tissues and corticosterone in rodents, therefore local level of active GCs can be set independently from systemic secretion driven by hypothalamo-pituitary-adrenal axis (HPA axis). Chronic systemic excess of GCs results in development of Cushing's syndrome which is characterised by central obesity and other metabolic disturbances. Despite normal serum levels of GCs, the patients with idiopathic obesity also develop metabolic syndrome. It was suggested that GCs could be elevated locally in target tissues due to enhanced 11HSD1 activity. This hypothesis was confirmed in transgenic rodent models. Prague hereditary hypertriglyceridemic (HHTg) rats represent a non-obese model of metabolic syndrome without genetic manipulations or specific mutations. The strain was bred by cross-mating of Wistar rat individuals with elevated serum levels of triglycerides (TGs). The strain exhibit hypertriglyceridemia and hypertension. When kept on high carbohydrate diet HHTg rats exhibit alterations in glucose homeostasis. Since there are no data that would describe...
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The role of glucocorticoids in circadian system
Tejkal, Karel ; Sumová, Alena (advisor) ; Forman, Martin (referee)
Glucocorticoids are mammalian steroid hormones secreted from the adrenal gland. The basal levels of glucocorticoids show a pronounced diurnal rhythm with maximum at the beginning of the active period and minimum at its end. Glucocorticoids have an influence over a variety of metabolic functions and their secretion is tightly regulated. This regulation also depends on the circadian system, which utilizes glucocorticoids to entrain the peripheral tissues by inducing rhythmic gene expression. The mechanisms by which glucocorticoids influence mammalian circadian system has not yet been precisely defined, especially concerning the influence of glucocorticoid signalling on gene expression in different tissues and the dynamics of glucocorticoid receptor (GR) occupancy. This thesis studies the influence of ablation of glucocorticoid signalization induced by adrenalectomy on the clock gene expression of in the central clock in the suprachiasmatic nucleus and peripheral clocks in the hippocampus and distal colon. The effect of adrenalectomy on gene expression is compared with the effect of restricting the feeding time, which has also been shown to affect glucocorticoid levels in the body. Other experiments were aimed at elucidating impact of changing the activity of GR on gene expression using synthetic GR...
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