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 vitamin D has been known for decades as vitamin D resistant rickets, caused by mutations of the gene encoding for vitamin D receptor (VDR). Findings of extra-skeletal effects of vitamin D and learning of the molecular mechanisms used by its biologically active metabolite calcitriol revealed other ways leading to its impaired sensitivity. Calcitriol takes advantage of both genomic and non-genomic mechanisms through its binding to vitamin D receptor, located not only in the cell nuclei but also in a perinuclear space. On the genomic level the complex of calcitriol bound to VDR binds to the DNA responsive elements of the controlled gene in concert with another nuclear receptor, retinoid X receptor, and expression of the VDR itself is controlled by its own ligand. These elements were found not only in the promotor region, but are scattered over the gene DNA. The gene expression includes a number of nuclear transcription factors which interact with the responsive elements and with each other and learning how they operate would further contribute to revealing causes of the impaired vitamin D sensitivity. Finally, the examples of major disorders are provided, associated with impairment of the vitamin D function and its receptor., L. Máčová, M. Bičíková, R. Hampl., and Obsahuje bibliografii
The paper presents the results of our effort to reveal objective parameters for evaluation of the spa treatment for patients with anxiety-depressive disorders. The study was based on our previous experience with neuroactive steroids and neurosteroids, which play a crucial role in the psychological well-being of patients by maintaining balance of the organism. A total number of 94 steroids were determinated in a group of 70 female patients diagnosed with anxiety-depressive disorders. Patients underwent a month spa treatment while maintaining unchanged medication dosing with SSRI (selective serotonin reuptake inhibitors). The other investigated factors contributing to improving the health of treated subjects were amino-acid homocysteine and serotonin. The blood samples were collected at the beginning and the end of the spa treatment. Serotonin in all patients increased by a relative 23 % (results given as relative differences in percent), while homocysteine decreased by 17.1 %. Statistically significant increases were found in 21 steroids, which indicate activation of the adrenal cortex. It can be assumed, that the overall improvement in the mental condition of patients, which was proved by questionnaire from Knobloch and Hausner, the increase in immune suppressive substances and anti-autoimmune responses, will maintain for a longer time after the spa treatment., M. Bicikova, L. Macova, L. Kolatorova, M. Hill, J. Novotny, D. Jandova, L. Starka., 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
The local concentration of glucocorticoids is intensively regulated by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD 1). Human 11β-HSD 1 also reversibly catalyzes the inter-conversion of 7α-hydroxy- and 7β-hydroxy-dehydroepiandrosterone (DHEA) into 7-oxo-DHEA. The cohort of 282 obese adolescents, 154 girls (median age 15.31 years, range 14.17-16.68 years) and 128 boys (median age 14.95 years, range 13.87-16.16 years), BMI (Body Mass Index) >90th percentile was examined. In samples collected before and after one month of reductive diet therapy, circulating levels of steroids were analyzed by liquid chromatography-tandem mass spectrometry and radioimmunoassay methods. The model of the treatment efficacy prediction was calculated. A significant reduction in circulating levels of cortisone, E2 and increased levels of 7β-hydroxy-DHEA after the reductive treatment was observed. Levels of cortisol, DHEA, DHT sustained without any significant change. The predictive Orthogonal Projections to Latent Structures (OPLS) model explained 20.1 % of variability of BMI, z-score change by the basal levels of 7α-hydroxy-DHEA, DHEA, cortisol and E2 as the strongest predictors. Reduced levels of circulating cortisone and reduced ratios of oxygenated/reduced metabolites reflect increased reductase activity of 11β-HSD 1 with reduced BMI, z-score. We hypothesize whether these changes can be attributed to the altered activity of 11β-HSD 1 in the liver., L. Máčová, L. Sosvorová, J. Vítků, M. Bičíková, M. Hill, H. Zamrazilová, B. Sedláčková, L. Stárka /., and Obsahuje bibliografii
The mood and behavior of individuals result from an orchestra of many factors. Among them steroids play an important role; however, only several common hormones have been investigated in this respect. It has been demonstrated that some steroid metabolites long considered merely the products of steroid hormone metabolism in fact possess considerable activity in the CNS. For this reason we studied the steroid metabolome including 50 analytes in 20 men with depression, 20 men with anxiety and 30 healthy controls. Significant differences were found not only between controls and men with either depression or anxiety, but also between men with depression and anxiety. Particularly striking were those steroids until now not generally associated with depression or anxiety, namely conjugated steroid forms, especially sulfates., M. Dušková, M. hill, M. Bičíková, M. Šrámková, D. Řípová, P. Mohr, L. Stárka., and Obsahuje bibliografii
Reduced levels of vitamin or its metabolites have been reported in various psychiatric disorders. Insufficient levels of vitamin D in depressive patients have been confirmed by many authors, but there have been conflicting results in subjects with anxiety disorders. In the present cross-sectional study, levels of calcidiol were determined in groups of depressive men and women and in men and women with anxiety disorders and compared with age matched controls. Significantly lower levels of calcidiol were found in men and women with depression as well as in age matched patients with anxiety disorders., M. Bičíková, M. Dušková, J. Vítků, B. Kalvachová, D. Řípová, P. Mohr, L. Stárka., and Obsahuje bibliografii
Vitamin D had been for a long time investigated for its effects on bone metabolism. Recently has been observed that the incidence of some neurodevelopmental disorders (including autism) increases hand in hand with vitamin D deficiency. Indeed, vitamin D was reported to modulate the biosynthesis of neurotransmitters and neurotrophic factors; moreover, its receptor was found in the central nervous system. Vitamin D deficiency was therefore assessed as a risk factor for autism, however the biological mechanism has not yet been revealed. In our review we focused on potential connections among vitamin D, steroids and autism. Potential mechanisms of vitamin D action are also discussed., L. Máčová, M. Bičíková, D. Ostatníková, M. Hill, L. Stárka., and Obsahuje bibliografii