Intrahepatic cholestasis of pregnancy (ICP) is a frequent liver disorder, mostly occurring in the third trimester. ICP is not harmful to the mothers but threatens the fetus. The authors evaluated steroid alterations in maternal and mixed umbilical blood to elucidate their role in the ICP development. Ten women with ICP were included in the study. Steroids in the maternal blood were measured by Gas Chromatography-Mass Spectrometry (GC-MS) (n=58) and RIA (n=5) at the diagnosis of ICP, labor, day 5 postpartum, week 3 postpartum and week 6 postpartum. The results were evaluated by ANOVA consisting of the subject factor, between subject factors ICP, gestational age at the diagnosis of ICP and gestational age at labor, withinsubject factor Stage and ICP × Stage interaction. The 17 controls were firstly examined in the week 36 of gestation. ICP patients showed reduced CYP17A1 activity in the C17,20 lyase step thus shifting the balance between the toxic conjugated pregnanediols and harmless sulfated 5α/β-reduced-17-oxo C19 steroids. Hence, more toxic metabolites originating in maternal liver from the placental pregnanes may penetrate backward to the fetal circulation. As these alterations persist in puerperium, the circulating steroids could be potentially used for predicting the predisposition to ICP even before next pregnancy., P. Šimják, M. Hill, A. Pařízek, L. Vítek, M. Velíková, M. Dušková, R. Kancheva, J. Bulant, M. Koucký, Z. Kokrdová, K. Adamcová, A. Černý, Z. Hájek, L. Stárka., and Obsahuje bibliografii
Melatonin plays a key role in the circadian timing system. At present, many other functions of melatonin are known. Question remains whether changes in endogenous melatonin may be associated with food intake. Hence, the levels of melatonin, C-peptide and glucose were followed during a daily regimen (16 hours) including standardized food intake using commercial kits. The diurnal profiles of the hormones and serum glucose were evaluated using ANOVA with Period and Subject as independent factors. Pearson’s correlations and using a multiple stepwise backward regression model consisting of the time factor as a polynomial, and serum C-peptide and glucose assessed the correlations between melatonin and the remaining parameters. Our results showed a significant negative correlation between melatonin and C-peptide. The profile of melatonin was physiological, decreasing after wake-up, showing minor changes during the daytime and increasing in the evening. As documented, lesser alterations were indicated in the course of the melatonin daytime profile, which may reflect periodic food intake. Food intake is not the primary factor influencing the melatonin course. While previous studies have mostly considered the protective effect of melatonin in diabetic subjects, our study brought the results suggesting food intake as a factor contributing to daytime melatonin variation in humans. However, the physiological role of melatonin association with food intake in daytime remains in question and should be further investigated., L. Stárka, M. Dušková, B. Rácz, K. Šimůnková, M. Hill, R. Kancheva., and Obsahuje bibliografii a bibliografické odkazy
n our study, 213 healthy Czech women aged 20 to 65 years were examined and divided into fully reproductive, premenopausal, menopausal and postmenopausal groups. In all subjects body composition was determined by classical anthropometry and metabolic profile was assessed. A total of 146 subjects completed 3-year longitudinal study. Total and LDL cholesterol increased and ratio HDL/total cholesterol decreased with age (p<0.001), most significantly in menopause. Triacylglycerols increased only up to menopause. HDL had a very slight trend to decrease in menopause and postmenopause. Fasting blood glucose level increased progressively (p<0.001), in postmenopause frequently exceeded normal range. Higher BMI, total fat mass and central fat indices were associated with higher total and LDL cholesterol, triacylglycerols, C-peptide, insulin and fasting blood glucose level (p<0.001; fasting blood glucose level to waist-to-hip ratio: p<0.01) and lower HDL cholesterol (p<0.001). Higher C-peptide and insulin were associated with lower HDL cholesterol and higher triacylglycerols (p<0.001). Fasting glucose correlated with LD L cholesterol (p<0.01). Higher SHBG was associated with higher HDL and lower LDL cholesterol (p<0.001). Hormone replacement treatment was related to lower fasting blood glucose level in postmenopausal women (p<0.01). Oral contraception is suggestive of a positive influence on lipid spectrum by increasing the ratio HDL/total cholesterol. Markers of lipid and carbohydrate metabolism are not only age-related, but they are also related to BMI, total fat mass and central fat indices. Therefore, preventive programs should be focused above all on menopausal women., I. Kosková, R. Petrásek, K. Vondra, M. Dušková, L. Stárka., and Obsahuje bibliografii
Parabens are a group of chemicals used as preservatives in the food, cosmetic and pharmaceutical industries. They are known to possess estrogenic effects, and therefore have been classified as endocrine disruptors. In addition to the classical endocrine organs, other tissues have endocrine activity, including adipose tissue. Several chemicals are known to cause obesogenic effects, and parabens are currently being studied in this context. The aim of this study was to investigate the possible connections of paraben exposure and obesity. Blood plasma from 27 healthy women was collected during their menstrual cycle. Basal anthropometric measures, levels of parabens (methylparaben, ethylparaben and propylparaben), adipokines (adiponectin, adipsin, leptin, resistin and visfatin) and hormones affecting energy balance and metabolic health (c-peptide, ghreline, GIP, GLP-1, glucagon, insulin, PAI-1) were measured. A Kolmogorov- Smirnov test showed higher methylparaben and propylparaben levels in women with BMI 25-34.9 compared to those with BMI 18.5-24.9. Plasma levels of methylparaben as well as the sum of parabens were positively associated with the plasma adipsin levels. Negative associations for methylparaben were found for glucagon, leptin and PAI-1. In accordance with other experimental studies we observed important associations of methylparaben and hormones affecting energy balance and metabolic health, indicating its obesogenic potential., L. Kolatorova, M. Sramkova, J. Vitku, J. Vcelak, O. Lischkova, L. Starka, M. Duskova., and Obsahuje bibliografii
Endocrine disruptors (EDs) are known to have harmful effects on the human endocrine system; special effort is actually given to the exposure during pregnancy. Humans are usually exposed to a mixture of EDs, which may potentiate or antagonize each other, and the combined effect may be difficult to estimate. The main phthalate monoesters monoethyl-, mono-n -butyl-, monoisobutyl-, monobenzyl-, mono-(2-ethylhexyl)-, mono-(2- ethyl-5-hydroxyhexyl)- and mono-(2-ethyl-5-oxohexyl) phthalate were determined in 18 maternal (37th week of pregnancy) and cord plasma samples using liquid chromatography-tandem mass spectrometry. Previously determined levels of selected bisphenols, parabens and steroids were also considered in this study. In cord blood, there were significantly higher mono-n-butyl phthalate levels than in maternal blood (p=0.043). The results of multiple regression models showed that maternal plasma phthalates were negatively associated with cord plasma androstenedione, testosterone and dehydroepiandrosterone and positively associated with estradiol and estriol. For estriol, a cumulative association was also observed for Σbisphenols. To the best of our knowledge, this is the first pilot study evaluating the effect of prenatal exposure by multiple EDs on newborn steroidogenesis. Our results confirmed phthalate accumulation in the fetal area and disruption of fetal steroidogenesis. This preliminary study highlights the negative impacts of in utero EDs exposure on fetal steroidogenesis., L. Kolatorova, J. Vitku, A. Vavrous, R. Hampl, K. Adamcova, M. Simkova, A. Parizek, L. Starka, M. Duskova., and Obsahuje bibliografii
In modern societies, living organisms are exposed daily to multiform pollution from industrial chemical products. Some of these substances have been shown to affect the endocrine system, and have been termed endocrine disruptors (EDs). Bisphenol A (BPA), which can leach from plastics, and parabens, used in cosmetic products, are among the most well-studied. Prenatal development is a vulnerable phase of human life, and disruptions during this period may have lifelong consequences. Since EDs are known to cross the placental barrier and BPA may accumulate in the fetus, "BPA-free" products have been introduced to the market. However, such products often contain alternative bisphenols (e.g. BPS, BPF) that have not yet been extensively examined or regulated. Moreover, alternative bisphenols often occur together with BPA. The human organism is thus exposed to a mixture of EDs, some of which can have additive or synergic effects. Recent findings have also shown that paraben exposure can alter bisphenol pharmacokinetics. Taking into account the widespread occurrence of various EDs and the potential multiplicity of their effects, doses of EDs currently considered safe may not actually be as safe as they appear, especially during pregnancy., L. Kolatorova, M. Duskova, J. Vitku, L. Starka., and Obsahuje bibliografii
Determination of response of cortisol and its metabolites to different stimuli may be important for adrenal gland disorders. To date, only one metabolite, cortisone, has been followed in stimulation tests of the adrenal gland. We aimed to describe a response of cortisol metabolites to the standard short Synacthen test (HDST), insulin tolerance test (ITT), low dose Synacthen test (LDST) and medium dose Synacthen test (MDST). Sixty healthy subjects were investigated: 30 men and 30 women. Plasma for measurements of cortisol and its metabolites was obtained before and 30th and 60th min after Synacthen and insulin administration. The cut-off 500 nmol/l of cortisol was reached after stimulation in all of tests, the maximal stimulation level was reached in 60th min in all of the tests except for LDST. The response of cortisol and its metabolites at 30th and 60th min strongly correlated in all of the tests except for LDST. Cortisol and its metabolites increased after stimulation; in contrast, cortisone and its metabolites decreased. We showed that the response of the cortisol metabolites during the Synacthen tests and ITT well correlated, and the MDST showed similar response compared to HDST. The decrease in cortisone metabolites may correspond to the regeneration of cortisol from cortisone in response to stimulation test., K. Simunkova, M. Duskova, M. Kosak, M. Krsek, V. Hana, M. Hill, H. Jandikova, H. Pospisilova, M. Sramkova, E. Bifulco, L. Starka., and Obsahuje bibliografii
Progesterone, estrogens, androgens and glucocorticoids all play important roles during pregnancy, from implantation to delivery. Focusing on selected steroid hormones in the peripartum period, we defined reference ranges measured using LS-MS/MS, and assessed relationships with maternal age, pregnancy weight gain, delivery type, and fetal sex. Samples were taken from 142 healthy women with physiological gravidity at the 37th week, during the first period of labor, and from newborn mixed cord blood. We found higher cortisol and 17-OH-pregnenolone plasma levels in mothers at the 37th week that carried male fetuses (p=0.03), but no significant differences in any studied hormones in newborns of different sex. Neither maternal age nor weight gain nor newborn birth weight had any relationships to any of the studied hormones. However, there were differences depending on vaginal versus planned cesarean section deliveries. In women carrying a male fetus we found significantly higher levels of 17-OH-pregnenolone, progesterone, cortisol, corticosterone and significantly lower levels of estradiol in those undergoing spontaneous vaginal delivery. However, we found no significant differences in the cord blood of newborn males from either delivery type. We established reference ranges for our analysis methods, which should be useful for further studies as well as in standard clinical practice., K. Adamcová, L. Kolátorová, T. Škodová, M. Šimková, A. Pařízek, L. Stárka, M. Dušková., and Obsahuje bibliografii
Postpartum depression affects 10-15 % women after childbirth. There is no currently generally accepted theory about the causes and mechanisms of postpartum mental disorders. The principal hypothesis concerns the association with sudden changes in the production of hormones affecting the nervous system of the mother and, on the other hand, with the ability of receptor systems to adapt to these changes. We observed changes in steroidogenesis in the period ar ound spontaneous delivery. We collected three samples of maternal blood. The first sampling was 4 weeks prior to term; the second sampling was after the onset of uterine contractions (the beginning of spontaneous labour); the third sampling was during the third stage of labour (immediately after childbirth). Additionally, we collected mixed umbilical cord blood. The almost complete steroid metabolome was analyzed by gas chroma tography-mass spectrometry followed by RIA for some steroids. Mental changes in women in the peripartum period were observed using the Hamilton Depression Rating Scale. The local Ethics Committee approved the study. We found already th e changes in androgens levels correlating with postpartum mood disorders four weeks prior to childbirth. The strongest correlations between steroid and postpartum mood change were found in venous blood samples collected from mothers after childbirth and from umbilical cord blood. The main role played testosterone, possibly of maternal origin, and estrogens originating from the fetal compartment. These results suggest that change s in both maternal and fetal steroidogenesis are involved in the development of mental changes in the postpartum period. Descriptions of changes in steroidogenesis in relation to po stpartum depression could help clarify the causes of this disease, and changes in some steroid hormones are a promising marker of mental changes in the postpartum period., A. Pařízek, M. Mikešová, R: Jirák, M. Hill, M. Koucký, A. Pašková, M. Velíková, K. Adamcová, M. Šrámková, H. Jandíková, M. Dušková, L. Stárka., and Obsahuje bibliografii
Taste is important for food intake. The fetus first experiences taste through amniotic fluid, and later via mother’s milk. Early human experience with taste has a key importance for later acceptance of food. Dietary behavior is determined by the interaction of many different factors. The development of the olfactory and taste receptors begins at 7-8 weeks of gestation. An early sensitive period probably exists when flavor preference is established. Sweet taste is preferred in early childhood; this is the reason why children are at increased risk of over-consuming saccharides. Gustatory sensitivity declines with age. The threshold for the perception of each basic taste differs, and is established genetically. In this review, we summarize published data on taste preferences and its development and changes during life., Š. Podzimek, M. Dušková, Z. Broukal, B. Rácz, L. Stárka, J. Dušková., and Obsahuje bibliografii