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Less common metabolites of steroid hormones in human physiology and pathophysiology Not long ago, they have been less common steroid metabolites regarded as mere degradation products of steroid metabolism. Since the last decades, it has been discovered that these substances, which are occurring in the human organism at Nano molar concentrations, are involved in the regulation of physiological processes, such as the immune response, thermoregulation, development of cancer and activity against the major steroids. As the introduction, the presented thesis provides an overview of published data dealing with the less common metabolites of steroids. Experimental part is based on partial studies whose objectives were chosen in such a way to help reveal some of the missing intermediate steps in the mechanism of steroid hormones action. Because these steroids occur in only Nano molar concentrations, the highly sensitive and specific methods such as radio-immuno assay (RIA), gas chromatography combined with mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) had to be used. In the case of metabolites 16α-hydroxy-dehydroepiandrosterone and 7-oxo- dehydroepiandrosterone, we developed and statistically evaluated two novel RIA methods. These rapid and sensitive methods suitable for...

The thesis focuses on selected, yet unsolved question of the role of less common steroids and SHBG as a junction of three endocrine systems. Answering these questions may help to understand the complex mechanism of action of these hormones on the human organism. This thesis is based on five author and co-written studies mostly published in foreign scientific journals. In the case of studies of metabolites 16α-OH-DHEA and 7-oxo-DHEA (Zamrazilová et al., 2007; Kazihnitková et al., 2007) were focused on the development of appropriate methodological approach because recently used methods showed a low sensitivity and specificity. We developed and statistically evaluated new RIA methods which are rapid, sensitive and inexpensive. Both of them can be used in other research even in routine practice. New methods were also used to determine the metabolites in a statistically significant sample of healthy human population. In another study (Zamrazilová et al., 2010) we examined the relationships of selected steroid metabolites and SHBG in patients with CAH. We assumed that SHBG may act as a non-steroidal laboratory parameter reflecting the effectiveness of substitution therapy in these patients. Our assumption was not confirmed. We observed lower levels of SHBG which at least in women reflect effects of...

Vitamin D is known for its role in the regulation of the metabolism of minerals in the body. Its deficiency is mainly associated with rickets and osteomalacia, characterized by defects in bone growth and development. However, the limits of this hormone's action extend much further. It can influence the differentiation of immune cells, thereby regulating the immune response and cell proliferation. After the discovery of its immunoregulatory functions, vitamin D became a hot candidate for the treatment of autoimmune diseases, such as multiple sclerosis, systemic lupus erythematosus, or diabetes mellitus. Furthermore, vitamin D was found to exhibit a suppressive effect on cancer cells. Vitamin D deficiency is a risk factor associated with the development of encephalomyelitis, schizophrenia, autism, and cardiovascular diseases. Currently, vitamin D analogs are being developed that are just as effective but do not affect calcium metabolism, thus eliminating the toxic effect of high doses of vitamin D. Key words: vitamin D3, 25-hydroxyvitamin D3, 25(OH)D3, cholecalciferol, 1α,25-dihydroxyvitamin D3, 1,25(OH)2D3, calcitriol, immunity, immunoregulatory function, vitamin D deficiency, autoimmune disease