The aim of our work was to provide data from women of fertile age with type 1 diabetes mellitus about the endogenous androgens and on their relations to the parameters of diabetes control. Forty-two women were examined, they did not use contraceptives for at least three months prior to the examination. A multivariate regression analysis showed that the daily insulin dose, the fasting glycemia and the HbA1c values and patient´s age correlated negatively with dehydroepiandrosterone sulfate, dehydroepiandrosterone and prolactin levels. The testosterone/ dehydroepiandrosterone sulfate ratio correlated positively with daily insulin dose and patient´s age. In contrast to adrenal androgens the values of other hormones, including total and free testosterone, androstenedione, dihydrotestosterone, estradiol, LH, FSH, 17-OH-P, progesterone and cortisol revealed no significant correlation. To conclude, significant relations between the glucose control parameters and the adrenal androgens and prolactin were demonstrated. These relationships should be considered as an important factor influencing diabetes control so the additional cardiovascular risk in women with DM1., H. Kvasnickova, R. Hampl, K. Vondra., and Obsahuje bibliografii
The general population is potentially exposed to many chemicals that can affect the endocrine system. These substances are called endocrine disruptors (EDs), and among them bisphenol A (BPA) is one of the most widely used and well studied. Nonetheless, there are still no data on simultaneous measurements of various EDs along with steroids directly in the seminal fluid, where deleterious effects of EDs on spermatogenesis and steroidogenesis are assumed. We determined levels of BPA and 3 estrogens using LC-MS/MS in the plasma and seminal plasma of 174 men with different degrees of infertility. These men were divided according their spermiogram values into 4 groups: (1) healthy men, and (2) slightly, (3) moderate, and (4) severely infertile men. Estradiol levels differed across the groups and body fluids. Slightly infertile men have significantly higher BPA plasma and seminal plasma levels in comparison with healthy men (p<0.05 and p<0.01, respectively). Furthermore, seminal BPA, but not plasma BPA, was negatively associated with sperm concentration and total sperm count (-0.27; p<0.001 and -0.24; p<0.01, respectively). These findings point to the importance of seminal plasma in BPA research. Overall, a disruption of estrogen metabolism was observed together with a weak but significant impact of BPA on sperm count and concentration., J. Vitku, L. Sosvorova, T. Chlupacova, R. Hampl, M. Hill, V. Sobotka, J. Heracek, M. Bicikova, L. Starka., and Obsahuje bibliografii
Hormones exert many actions in the brain. Their access and effects in the brain are regulated by the blood-brain barrier (BBB). Hormones as other substances may enter the brain and vice versa either by paracellular way requiring breaching tight junctions stitching the endothelial cells composing the BBB, or by passage through the cells (transcellular way). Hormones influence both ways through their receptors, both membrane and intracellular, present on/in the BBB. In the review the main examples are outlined how hormones influence the expression and function of proteins forming the tight junctions, as well as how they regulate expression and function of major protein transporters mediating transport of various substances including hormone themselves., R. Hampl, M. Bičíková, L. Sosvorová., and Obsahuje bibliografii
Resistance to steroid hormones presents a serious problem with respect to their mass use in therapy. It may be caused genetically by mutation of genes involved in hormonal signaling, not only steroid receptors, but also other players in the signaling cascade as co-regulators and other nuclear factors, mediating the hormone-born signal. Another possibility is acquired resistance which may develop under long-term steroid treatment, of which a particular case is down regulation of the receptors. In the review recent knowledge is summarized on the mechanism of main steroid hormone action, pointing to already proven or potential sites causing steroid resistance. We have attempted to address following questions: 1) What does stay behind differences among patients as to their response to the (anti)steroid treatment? 2) Why do various tissues/cells respond differently to the same steroid hormone though they contain the same receptors? 3) Are such differences genetically dependent? The main attention was devoted to glucocorticoids as the most frequently used steroid therapeutics. Further, androgen insensitivity is discussed with a particular attention to acquired resistance to androgen deprivation therapy of prostate cancer. Finally the potential causes are outlined of breast and related cancer(s) resistance to antiestrogen therapy., R. Hampl, K. Vondra., and Obsahuje bibliografii
Normal pressure hydrocephalus (NPH) is one of a few treatable conditions of cognitive decline affecting predominately elderly people. Treatment, commonly based on the ventriculoperitoneal shunt insertion, leads to a partial or complete correction of patient's state, although its effect does not unfortunately always last. The aim of our study was to observe the changes of homocysteine and selected steroids and neurosteroids and follow-up the patients with respect to the duration of the NPH-related dementia improvement. The cerebrospinal fluid and plasma levels of cortisol, cortisone, dehydroepiandrosterone (DHEA), 7α-hydroxy-DHEA, 7β-hydroxy-DHEA, 7-oxo-DHEA, 16α-hydroxy-DHEA (all LC-MS/MS), DHEA-sulphate (DHEAS) (radioimmunoassay) and homocysteine (gas chromatography) were determined in NPH-diagnosed subjects before, during and 6, 12 and 24 months after shunt insertion. The cognitive functions ameliorated after shunt insertion and remain improved within 2 years. Changes in cerebrospinal fluid DHEAS, DHEA and its ratio, cortisone/cortisol and 16α-hydroxy-DHEA and plasma DHEAS, 7β-hydroxy-DHEA, cortisone/cortisol and homocysteine were found. Mentioned changes may contribute to the clarification of NPH pathogenesis. Altered neurosteroids levels are possible indicators to be utilized in the follow-up of NPH subjects. Moreover, plasma homocysteine may serve as an early indicator of NPH-related dementia., L. Sosvorova, M. Mohapl, M. Hill, L. Starka, M. Bicikova, J. Vitku, R. Kanceva, J. Bestak, R. Hampl., and Obsahuje bibliografii
Cytokines are widely known mediators of inflammation accompanying many neurodegenerative disorders including normal pressure hydrocephalus (NPH). NPH is caused by impaired cerebrospinal fluid (CSF) reabsorption and treated by surgical shunt insertion. The diagnostics is still complicated and the shunt effect is not durable; after several years, dementia may develop. In the clinical practice, biomarkers support the diagnostics as well as the further time course of many neurodegenerative diseases. Until recently, no reliable biomarker for NPH was evaluated. The attempt of this review was to make a survey concerning cytokines as possible NPH markers. Among all reviewed cytokines, the most promising are CSF IL-10 and IL-33, enabling to follow-up the disease progression and monitoring the effectiveness of the shunt insertion., L. Sosvorova, M. Mohapl, J. Vcelak, M. Hill, J. Vitku, R. Hampl., and Obsahuje bibliografii
In this review we summarize recent opinions on the possible role of vitamin D in the risk of thyroid diseases development. It may be concluded from the available data that vitamin D deficiency, particularly levels below 12.5 ng/ml should be considered as an additional, but important risk factor for development of thyroid autoimmunity, both chronic autoimmune thyroiditis and Graves´ disease. A higher risk of Graves´ disease development is also associated with several polymorphisms in the gene encoding for vitamin D binding protein and for the specific receptor of active form of vitamin D - 1,25-(OH)2D3 in the respective target cells. Important for development of thyroid cancer appeared polymorphisms of genes encoding for vitamin D receptors and of genes encoding for the participating hydroxylating enzymes in thyroid tissue, leading to a diminished local 1,25-(OH)2D3 formation capacity with following alteration of antiproliferatory, antiapoptotic and prodifferentiating efficacy of the latter. Whether supplementation with high doses of vitamin D or its analogues possesses preventive or therapeutic effect is an object of intensive studies., K. Vondra, L. Stárka, R. Hampl., and Obsahuje bibliografii
In women with chronic autoimmune thyroiditis and vitamin D deficiency we have found reference levels of relevant metabolichormonal parameters except for parathormone and total calcium. Three months supplementation with vitamin D (4300 IU/day, cholekalciferol) did not lead to significant changes of investigated hormonal parameters, while the levels of parathormone and calcium reached normal levels. However, a correlation analysis revealed marked changes in mutual relations. First, an inverse correlation of vitamin D with parathormone, insulin secretion (C peptide, insulin) and its efficiency (HOMA IR) disappeared. Relationships of vitamin D to hepatic insulin resistance (insulin/C peptide), to DHEA (both negative), and to DHEAS/DHEA ratio (positive) were newly found. Second, a positive correlation of CRP with insulin secretion remained, while its relation to insulin efficiency (HOMA IR, insulin/ C peptide) was newly observed. Analogical positive correlations appeared also among anti TPO and insulinemia, insulin/C peptide, HOMA IR, and anti Tg to C peptide. A relationship of the CRP with anti TPO became significant (+). Third, out of glucose metabolism parameters only insulin/C peptide and glycemia did not correlate with vitamin D during its deficiency, while after supplementation insulin/ C peptide alone correlated positively with both DHEAS and DHEA, and negatively with vitamin D., K. Vondra, R. Bílek, P. Matucha, M. Salátová, M. Vosátková, L. Stárka, R. Hampl., and Obsahuje bibliografii