Dehydroepiandrosterone (DHEA) and its sulphate-bound form (DHEAS) are important steroids mainly of adrenal origin. Their physiological and pathophysiological functions are not yet fully identified, although a number of various possible features have been hypothesized. Most popular is the description of the “hormone of youth” as the long-term dynamics of DHEA levels are characterized by a sharp age-related decline in the late adulthood and later. Low levels of DHEA are, however, associated not only with the ageing process but also with diabetes mellitus, cardiovascular diseases and some neurological or immunological entities. In the past decade, a number of brief studies have concentrated on these relationships and also on the role of exogenous DHEA in health, disease and human well-being. This article tries to summarize some of the most important facts achieved recently., P. Celec, L. Stárka., and Obsahuje bibliografii
Dehydroepiandrosterone (DHEA) possesses fat-reducing effect, while little information is available on whether DHEA regulates cell proliferation and mitochondrial function, which would, in turn, affect lipid droplet accumulation in the broiler. In the present study, the lipid droplet accumulation, cell proliferation, cell cycle and mitochondrial membrane potential were analysis in primary chicken hepatocytes after DHEA treated. The results showed that total area and counts of lipid droplets were significantly decreased in hepatocytes treated with DHEA. The cell viability was significantly increased, while cell proliferation was significantly inhibited in a dose-dependent manner in primary chicken hepatocytes after DHEA treated. DHEA treatment significantly increased the cell population in S phase and decreased the population in G2/M in primary chicken hepatocytes. Meanwhile, the cyclin A and cyclin-dependent kinases 2 (CDK2) mRNA abundance were significantly decreased in hepatocytes after DHEA treated. No significant differences were observed in the number of mitochondria, while the mitochondrial membrane permeability and succinate dehydrogenase (SDH) activity were significantly increased in hepatocytes after DHEA treated. In conclusion, our results demonstrated that DHEA reduced lipid droplet accumulation by inhibiting hepatocytes proliferation and enhancing mitochondrial function in primary chicken hepatocytes., Long-Long Li, Dian Wang, Chong-Yang Ge, Lei Yu, Jin-Long Zhao, Hai-Tian Ma., and Obsahuje bibliografii
Immunomodulatory steroids, dehydroepiandrosterone and its 7-hydroxylated metabolites and sex hormone-binding globulin (SHBG) were determined in sera of 88 women aged 18-75 years. The group consisted of 34 healthy women, 37 women with subclinical and 17 women with manifest hypothyroidism. In all subjects the laboratory parameters of thyroid function (thyrotropin, free thyroxine and triiodothyronine) and thyroid autoantibodies to thyroid peroxidase and thyroglobulin were determined. The aim was to find out 1) whether the above steroids and SHBG levels differ in individual groups according to thyroid status, 2) whether correlations exist among investigated steroids and thyroid laboratory parameters, and 3) whether the respective steroid and SHBG levels differ according to the presence of principal thyroid autoantibodies. With the exception of 7β-hydroxy-dehydroepindrosterone levels, which were decreased in patients with manifest hypothyroidism (p<0.05), no significant differences in steroid and SHBG levels among groups according to diagnosis were found. On the other hand, significantly decreased levels of all the immunomodulatory steroids studied were found in subjects with positive titres of thyroid autoantibodies. This finding was supported by a tight negative correlation among the above steroids and thyroid autoantibodies. In addition, these steroids correlated negatively with thyrotropin and positively with free thyroid hormones. The results point to a negative relationship between the above mentioned immunoprotective steroids and the extent of the autoimmune process in hypothyroidism., K. Drbalová, P. Matucha, M. Matějková-Běhanová, R. Bílek, L. Kříž, H. Kazihnitková, R. Hampl., and Obsahuje bibliografii a bibliografické odkazy
Pulmonary hypertension is a group of disorders characterized by elevated mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance. To test our hypothesis that combining two drugs useful in experimental pulmonary hypertension, statins and dehydroepiandrosterone sulfate (DHEA-S), is more effective than either agent alone, we induced pulmonary hypertension in adult male rats by exposing them to hypoxia (10 %O2) for 3 weeks. We treated them with simvastatin (60 mg/l) and DHEA-S (100 mg/l) in drinking water, either alone or in combination. Both simvastatin and DHEA-S reduced mPAP (froma mean±s.d. of 34.4±4.4 to 27.6±5.9 and 26.7±4.8 mmHg, respectively), yet their combination was not more effective (26.7±7.9 mmHg). Differences in the degree of oxidative stress (indicated by malondialdehydeplasma concentration), the rate of superoxide production (electron paramagnetic resonance), or blood nitric oxide levels (chemiluminescence) did not explain the lack of additivity of the effect of DHEA-S and simvastatin on pulmonary hypertension. We propose that the main mechanism of both drugs on pulmonary hypertension could be their inhibitory effect on 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, which could explain their lack of additivity.
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
Nearly 60 years has elapsed since the first isolation and identification of 7α-hydroxy-dehydroepiandrosterone, and in that time much information has been gained on its occurrence, metabolism, ontogeny, immunomodulatory activity, cell proliferation, cortisol control in local tissues and neuroactivity. Additional knowledge about this steroid may elucidate its role in obesity, neurodegenerative disturbances such as Alzheimer’s disease, or psychiatric disorders such as schizophrenia or depression. This review aims to provide a comprehensive summary of the available literature on 7α-hydroxydehydroepiandrosterone., 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