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Inflammation and peripheral metabolism of glucocorticoids
Leden, Pavel ; Kment, Milan (advisor) ; Hampl, Richard (referee) ; Kršek, Michal (referee)
10 Abstract Glucocorticoids play an important role in regulation of inflammation and their immunosuppressive effect is widely used for treatment of inflammatory diseases. The biological activity of glucocorticoids depends not only on their plasma concentrations, the number of receptors and the responsiveness of the target cells but also on the local metabolism of glucocorticoids that is predominated by 11β-hydroxysteroid dehydrogenase (11HSD). Two isoforms of 11HSD are known. The isoform 11HSD1 operates in vivo predominantly as a reductase that increases the local concentrations of glucocorticoids by reduction of their 11-oxo derivatives. The isoform 11HSD2 is a pure dehydrogenase that inactivates biologically active glucocorticoids to their inactive 11-oxo derivatives. The published data concerning peripheral metabolism of glucocorticoids during inflammation were obtained mostly in in-vitro studies. The aim of the thesis therefore was: (1) to study peripheral metabolism of glucocorticoids during trinitrobenzensulfonic acid (TNBS) induced colitis in rat. (2) to study peripheral metabolism of glucocorticoids in biopsies from human ulcerative colitis (3) to examine peripheral metabolism of glucocorticoids during dextran sodium sulphate (DSS) induced colitis in rat and (4) to study peripheral metabolism of...
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Physiologic and pathophysiologic aspects of selected endocrinopathies. Their relationship to adipose tissue matebolism and insulin resistance
Ďurovcová, Viktória ; Kršek, Michal (advisor) ; Saudek, František (referee) ; Štich, Vladimír (referee)
The pathogenesis of insulin resistance is a complex and still intensively studied issue. Endocrine and paracrine activity of the adipose tissue together with mi- tochondrial dysfunction are the most discussed potential factors included in the development of insulin resistance. In the first part of our study we examined the involvement of the adipose tissue and its secretory products in the etiopathogenesis of insulin resistance in patients with Cushing's syndrome, acromegaly and simple obesity. We focused on three important regulators of metabolic homeostasis - fibroblast growth factors 21 and 19 (FGF-21 and FGF-19) and adipocyte fatty acid binding protein (FABP-4). We found significantly elevated circulating levels of FGF-21 and FABP-4 ac- companying insulin resistance in both patients with simple obesity and patients with obesity connected to Cushing's syndrome, as compared to healthy controls. The concentrations of both substances were comparable between hypercortisolic and obese patients. This finding together with the absence of correlation be- tween the levels of FGF-21 resp. FABP-4 and cortisol suggest that the reason for elevation of their concentrations is obesity and its metabolic consequences themselves rather then the effect of hypercortisolism on FGF-21 and FABP-4 production. We found no...
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Other factors influencing daytime melatonin levels.
Rácz, Beáta ; Vondra, Karel (advisor) ; Kršek, Michal (referee) ; Sumová, Alena (referee)
Circadian rhythms are important for the adaptation of the organism to the changes of the environment. The internal biological clock (pacemaker) has a rhythm which is slightly longer or shorter than 24 hours. Melatonin is a pineal hormone produced during the dark period. The gastrointestinal tract is the main extrapineal source and the main source of melatonin during the light period. There are missing studies which are focused on the effects of the food on steroid hormones. Aim: To elucidate the effect of the food on selected hormone levels in two consequent studies of eight healthy nonsmoker premenopausal women in follicular phase of their menstrual cycle. Results: 1) 16 hours long monitoring: The levels of melatonin decreased significantly two hours after lunch. Cortisol levels were decreasing throughout the whole day and an additional decrease was found two hours after lunch. We were the first to report the significant connections of estradiol and SHBG to food intake. 2) Monitoring after different stimuli: Levels of melatonin increased 40 minutes after the i.v. application of glucose. In oGTT this increase was slower. Cortisol has decreased after the application of glucose, more apparently after its i.v. application. The breakfast led to increase of cortisol levels. OGTT and i.v.GTT caused some...
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Acipimox during Short-Term Exercise Exerts A Negative Feedback of Growth Hormone on Ghrelin Secretion in Patients with Bulimia Nervosa and in Healthy Women: The Role of Lipolysis
Smitka, Kvido ; Nedvídková, Jara (advisor) ; Kršek, Michal (referee) ; Čáp, Jan (referee)
Title: Acipimox during Short-Term Exercise Exerts A Negative Feedback of Growth Hormone on Ghrelin Secretion in Patients with Bulimia Nervosa and in Healthy Women: The Role of Lipolysis Objective: Eating disorders, such as bulimia nervosa (BN) and anorexia nervosa (AN), are characterized by abnormal eating behavior. The main features of BN are binge-eating and inappropriate compensatory methods to prevent weight gain. The appetite-modulating peptide ghrelin is secreted by the stomach and shows a strong release of growth hormone (GH). A potential GH-ghrelin feedback loop between stomach and the pituitary has been recently reported. Acipimox (Aci), an analogue of nicotinic acid, inhibits lipolysis in adipose tissue (AT) and reduces plasma glycerol and free fatty acids (FFA) levels. Exercise and Aci are stimulators of GH secretion. We suppose that a negative feedback from increased GH levels during exercise may play a role in reducing plasma ghrelin levels. We surmised that altered baseline activity and exercise-induced activation of the sympathetic nervous system (SNS) results in excessive stimulation of lipolysis associated with negative energy balance and may lead to abnormal AT metabolism in patients with BN. Disruption of the gut-brain-AT axis might be involved in the pathogenesis of BN. The...
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Other factors influencing daytime melatonin levels.
Rácz, Beáta ; Vondra, Karel (advisor) ; Kršek, Michal (referee) ; Sumová, Alena (referee)
Circadian rhythms are important for the adaptation of the organism to the changes of the environment. The internal biological clock (pacemaker) has a rhythm which is slightly longer or shorter than 24 hours. Melatonin is a pineal hormone produced during the dark period. The gastrointestinal tract is the main extrapineal source and the main source of melatonin during the light period. There are missing studies which are focused on the effects of the food on steroid hormones. Aim: To elucidate the effect of the food on selected hormone levels in two consequent studies of eight healthy nonsmoker premenopausal women in follicular phase of their menstrual cycle. Results: 1) 16 hours long monitoring: The levels of melatonin decreased significantly two hours after lunch. Cortisol levels were decreasing throughout the whole day and an additional decrease was found two hours after lunch. We were the first to report the significant connections of estradiol and SHBG to food intake. 2) Monitoring after different stimuli: Levels of melatonin increased 40 minutes after the i.v. application of glucose. In oGTT this increase was slower. Cortisol has decreased after the application of glucose, more apparently after its i.v. application. The breakfast led to increase of cortisol levels. OGTT and i.v.GTT caused some...
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Physiologic and pathophysiologic aspects of selected endocrinopathies. Their relationship to adipose tissue matebolism and insulin resistance
Ďurovcová, Viktória ; Kršek, Michal (advisor) ; Saudek, František (referee) ; Štich, Vladimír (referee)
The pathogenesis of insulin resistance is a complex and still intensively studied issue. Endocrine and paracrine activity of the adipose tissue together with mi- tochondrial dysfunction are the most discussed potential factors included in the development of insulin resistance. In the first part of our study we examined the involvement of the adipose tissue and its secretory products in the etiopathogenesis of insulin resistance in patients with Cushing's syndrome, acromegaly and simple obesity. We focused on three important regulators of metabolic homeostasis - fibroblast growth factors 21 and 19 (FGF-21 and FGF-19) and adipocyte fatty acid binding protein (FABP-4). We found significantly elevated circulating levels of FGF-21 and FABP-4 ac- companying insulin resistance in both patients with simple obesity and patients with obesity connected to Cushing's syndrome, as compared to healthy controls. The concentrations of both substances were comparable between hypercortisolic and obese patients. This finding together with the absence of correlation be- tween the levels of FGF-21 resp. FABP-4 and cortisol suggest that the reason for elevation of their concentrations is obesity and its metabolic consequences themselves rather then the effect of hypercortisolism on FGF-21 and FABP-4 production. We found no...
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Neuroactive steroids and addictions
Jandíková, Hana ; Vondra, Karel (advisor) ; Miovský, Michal (referee) ; Kršek, Michal (referee)
Neuroactive steroids are a group of steroid hormones which act non-genomically to influence the neuron excitability of neuronal synapses. Addictive substances can interfere with the synthesis of neuroactive steroids through many mechanisms, affecting their levels and changing their functionality. At the same time, neuroactive steroids play a role in the development of addiction, since their levels change during attempts to quit and therefore affect the success of treatments for addiction. This study focuses on the relationships between individual addictive substances and neuroactive steroids, the individual functional mechanisms and how they influence each other. It is generally known that addictive substances result in the release of anxiolytics that act on neuroactive steroids. This plays a role in the development of addiction. We also describe in detail the effect of smoking on steroid hormones and the endocrine system in general. Using tobacco addition as a model, we studied the relationship between addiction and neuroactive steroids. As part of my doctoral studies we performed a prospective study that followed changes in the steroid spectra induced by smoking as well as when quitting smoking. We also developed a predictive model to predict the likelihood of success in treating tobacco...
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Inflammation and peripheral metabolism of glucocorticoids
Leden, Pavel ; Kment, Milan (advisor) ; Hampl, Richard (referee) ; Kršek, Michal (referee)
10 Abstract Glucocorticoids play an important role in regulation of inflammation and their immunosuppressive effect is widely used for treatment of inflammatory diseases. The biological activity of glucocorticoids depends not only on their plasma concentrations, the number of receptors and the responsiveness of the target cells but also on the local metabolism of glucocorticoids that is predominated by 11β-hydroxysteroid dehydrogenase (11HSD). Two isoforms of 11HSD are known. The isoform 11HSD1 operates in vivo predominantly as a reductase that increases the local concentrations of glucocorticoids by reduction of their 11-oxo derivatives. The isoform 11HSD2 is a pure dehydrogenase that inactivates biologically active glucocorticoids to their inactive 11-oxo derivatives. The published data concerning peripheral metabolism of glucocorticoids during inflammation were obtained mostly in in-vitro studies. The aim of the thesis therefore was: (1) to study peripheral metabolism of glucocorticoids during trinitrobenzensulfonic acid (TNBS) induced colitis in rat. (2) to study peripheral metabolism of glucocorticoids in biopsies from human ulcerative colitis (3) to examine peripheral metabolism of glucocorticoids during dextran sodium sulphate (DSS) induced colitis in rat and (4) to study peripheral metabolism of...
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Acipimox during Short-Term Exercise Exerts A Negative Feedback of Growth Hormone on Ghrelin Secretion in Patients with Bulimia Nervosa and in Healthy Women: The Role of Lipolysis
Smitka, Kvido ; Nedvídková, Jara (advisor) ; Kršek, Michal (referee) ; Čáp, Jan (referee)
Title: Acipimox during Short-Term Exercise Exerts A Negative Feedback of Growth Hormone on Ghrelin Secretion in Patients with Bulimia Nervosa and in Healthy Women: The Role of Lipolysis Objective: Eating disorders, such as bulimia nervosa (BN) and anorexia nervosa (AN), are characterized by abnormal eating behavior. The main features of BN are binge-eating and inappropriate compensatory methods to prevent weight gain. The appetite-modulating peptide ghrelin is secreted by the stomach and shows a strong release of growth hormone (GH). A potential GH-ghrelin feedback loop between stomach and the pituitary has been recently reported. Acipimox (Aci), an analogue of nicotinic acid, inhibits lipolysis in adipose tissue (AT) and reduces plasma glycerol and free fatty acids (FFA) levels. Exercise and Aci are stimulators of GH secretion. We suppose that a negative feedback from increased GH levels during exercise may play a role in reducing plasma ghrelin levels. We surmised that altered baseline activity and exercise-induced activation of the sympathetic nervous system (SNS) results in excessive stimulation of lipolysis associated with negative energy balance and may lead to abnormal AT metabolism in patients with BN. Disruption of the gut-brain-AT axis might be involved in the pathogenesis of BN. The...
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