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Analysis and Biochemistry of Less Current Steroids - Neuroactive Steroids and Their Sulfates
Včeláková, Helena ; Hill, Martin (advisor) ; Ventura, Karel (referee) ; Meloun, Milan (referee)
Disertation work brings new findings in the field ofbiochemistry and analysis of neuroactive steroids. The pubrications invorved to the dissertation work dear with biochemicar anarysis of neuroactive steroids and its apprication in biomedicine. Some endogenous steroids can act as efficient neuromodurators' These substances are known as neuroactive steroids' If they are synthesized directly in the central nervous system, they have been named the neurosteroids (Schreiber 1980; corpechot, Rober et ar. rggl). some of the neuroactive steroids act as neuroactivators, the others are neuroinhibitors (Kimonides, Khatibi et al. l99g; Kaasik, Kalda et al. 2001; Lockhart, Warner et al. 2002). The neuroactive steroids operate usually as modulators of membrane receptors (GABA_ receptors and NMDA_receptors) responsible for the permeability of ion channels in neuronal cells. Generally, while physiologic functions and pharmacokinetics of endogenous neuroactive steroids studied on animals was investigated (Wang, Wahlstrom et al. 1997; Norberg, Backstrom et al. 19gg), the number of studies concerning neuroactive steroids in human body fluids and tissues in connection with physiology is insufficient (Bicikova, Tallova et al. 2000; Strohle, Romeo et al. 2003). The main problem is probably laboriousness of corresponding...
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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 Impact of Selected Endocrine Disruptors on Human Spermatogenesis
Vítků, Jana ; Hill, Martin (advisor) ; Pohanka, Michal (referee) ; Lapčík, Oldřich (referee)
Steroid hormones in testis play an important role in spermatogenesis, maintenance of the male reproductive tract, production of semen and the maintenance of secondary sex characteristics and libido. They are also discussed as a target for substances called endocrine disruptors (EDs). No complex study was conducted on evaluation of relationships between EDs and steroid spectrum in 2 biological fluids; seminal plasma and plasma. The aim of the PhD. thesis was to develop and validate a method for determination of bisphenol A (BPA) and steroid spectrum in plasma and seminal plasma and to shed more light into mechanisms of ED action and effects of BPA and polychlorinated biphenyls (PCBs) on human spermatogenesis and steroidogenesis. Two new liquid-chromatography mass spectrometry methods for determination of BPA and 11 steroids in plasma and seminal plasma were developed and validated. The methods were used for estimation of analyte concentrations in 191 men with a different degree of fertility. Concurrently, the levels of six congeners of PCBs, gonadotropins, selenium and zinc in plasma were estimated. Partial correlations adjusted for age and BMI were calculated to evaluate relationships between these analytes. Seminal BPA, but not plasma BPA, was negatively associated with sperm concentration...
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Steroid metabolome in human physiology and pathophysiology.
Hána, Václav ; Hill, Martin (advisor) ; Meloun, Milan (referee) ; Čáp, Jan (referee)
Many studies have shown steroid hormone changes in adrenal incidentalomas with subclinical hypercortisolism and various forms of Cushing's syndrome. The aim of our work was to measure, using novel steroid GC-MS/MS measurement procedure, complex picture of many steroids in these patients. With the knowledge of these changes we could better explain causal pathophysiologic changes. In the study on patients with adrenal incidentalomas we described complex steroid changes in patients with subclinical hypercortisolism. Previous studies showed decrease of DHEAS in subclinical hypercortisolism. We confirmed this finding and described a decrease in other androgens and their metabolites. We also evaluated their sensitivity and specificity when compared to routinely used parameters for diagnosis of subclinical hypercortisolism. Furthermore, we looked at the alterations in all measured steroids and their changes in the 1 mg dexamethasone suppression test. In another study, we analyzed steroid changes in various forms of Cushing's syndrome. We confirmed the decrease of adrenal androgens in the ACTH independent forms and mild increase in the ACTH dependent forms. We also described elevations of mineralocorticoid precursors in central and ectopic forms of ACTH secretion. In the distinction of ectopic and central...
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Analysis and Biochemistry of Less Current Steroids - Neuroactive Steroids and Their Sulfates
Včeláková, Helena ; Hill, Martin (advisor) ; Ventura, Karel (referee) ; Meloun, Milan (referee)
Disertation work brings new findings in the field ofbiochemistry and analysis of neuroactive steroids. The pubrications invorved to the dissertation work dear with biochemicar anarysis of neuroactive steroids and its apprication in biomedicine. Some endogenous steroids can act as efficient neuromodurators' These substances are known as neuroactive steroids' If they are synthesized directly in the central nervous system, they have been named the neurosteroids (Schreiber 1980; corpechot, Rober et ar. rggl). some of the neuroactive steroids act as neuroactivators, the others are neuroinhibitors (Kimonides, Khatibi et al. l99g; Kaasik, Kalda et al. 2001; Lockhart, Warner et al. 2002). The neuroactive steroids operate usually as modulators of membrane receptors (GABA_ receptors and NMDA_receptors) responsible for the permeability of ion channels in neuronal cells. Generally, while physiologic functions and pharmacokinetics of endogenous neuroactive steroids studied on animals was investigated (Wang, Wahlstrom et al. 1997; Norberg, Backstrom et al. 19gg), the number of studies concerning neuroactive steroids in human body fluids and tissues in connection with physiology is insufficient (Bicikova, Tallova et al. 2000; Strohle, Romeo et al. 2003). The main problem is probably laboriousness of corresponding...
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The Impact of Selected Endocrine Disruptors on Human Spermatogenesis
Vítků, Jana ; Hill, Martin (advisor) ; Pohanka, Michal (referee) ; Lapčík, Oldřich (referee)
Steroid hormones in testis play an important role in spermatogenesis, maintenance of the male reproductive tract, production of semen and the maintenance of secondary sex characteristics and libido. They are also discussed as a target for substances called endocrine disruptors (EDs). No complex study was conducted on evaluation of relationships between EDs and steroid spectrum in 2 biological fluids; seminal plasma and plasma. The aim of the PhD. thesis was to develop and validate a method for determination of bisphenol A (BPA) and steroid spectrum in plasma and seminal plasma and to shed more light into mechanisms of ED action and effects of BPA and polychlorinated biphenyls (PCBs) on human spermatogenesis and steroidogenesis. Two new liquid-chromatography mass spectrometry methods for determination of BPA and 11 steroids in plasma and seminal plasma were developed and validated. The methods were used for estimation of analyte concentrations in 191 men with a different degree of fertility. Concurrently, the levels of six congeners of PCBs, gonadotropins, selenium and zinc in plasma were estimated. Partial correlations adjusted for age and BMI were calculated to evaluate relationships between these analytes. Seminal BPA, but not plasma BPA, was negatively associated with sperm concentration...
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|
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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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