|
|
Synthesis of Steroidal Modulators for Bile Acid Receptors
Kašpar, Miroslav ; Kudová, Eva (advisor) ; Drašar, Pavel (referee) ; Kvasnica, Miroslav (referee)
The Thesis comprises three major projects. The first project is concerned with the creation of a pregnane compound library that can be used to explore the structure-activity relationship with the TGR5 and FXR receptors. The project draws structural inspiration from Sato's work and involves the compound characterization, digitization, computational methods, and biochemical analysis of a historic group collection of steroids. The second project focuses on the synthesis of modified bile acids using Grignard, Wittig, cross-coupling, or cycloaddition reactions. The synthesized compounds were tested for their TGR5 and FXR activity, leading to the discovery of (E)-7-ethylidene-3α-hydroxy-5β- cholan-24-oic acid, which is known to be the only bile acid with TGR5/FXR dual action. In the last part of the Thesis, 16 oxidizing agents were tested on 5 substrates for their selectivity in oxidizing axial or equatorial hydroxyl groups.
|
|
|
Significance of androgens of adrenal origin in polycystic ovary syndrome and hirsutism
Varausová, Anežka ; Vítků, Jana (advisor) ; Jansová, Denisa (referee)
The adrenal cortex is the source of a wide range of steroid hormones. Mineralocorticoids, glucocorticoids and, last but not least, androgens are synthesized here. The most abundant adrenal androgen is dehydroepiandrosterone sulfate, whose androgenic potency is not high, but it forms a reservoir in the circulation and can subsequently be metabolized to more potent androgens. Another androgen formed in the adrenal cortex is 11β-hydroxy-androstenedione. This steroid also has low androgenic potency, but its importance lies in the fact that it serves as a precursor of the active androgens - 11-oxygenated derivatives of testosterone and dihydrotestosterone. Besides their high androgenic potency, their relatively high levels in circulation prompt attention to be paid to these steroid hormones in all endocrine disorders where classical androgens are monitored. The determination of these androgens is suggested in polycystic ovary syndrome and idiopathic hirsutism, among others, where it could explain the discrepancy between the intensity of clinical symptoms and testosterone and dihydrotestosterone levels. The aim of this thesis is to review the scientific knowledge on the relationship between 11-oxygenated androgens and the mentioned endocrine disorders. Keywords: steroid, adrenal cortex, androgen,...
|
|
|
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...
|
|
|
The Impact of Selected Endocrine Disruptors on Human Spermatogenesis
Vítků, Jana
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...
|
|
|
The Impact of Selected Endocrine Disruptors on Human Spermatogenesis
Vítků, Jana
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...
|
|
|
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...
|
guest ::
