The objective of this study was to evaluate the influence of low-dose combined oral contraception (COC) on basal and stimulated (1 μg ACTH test) levels of serum and salivary cortisol (F), cortisone and on basal serum cortisol binding globulin (CBG), adrenocorticotropic hormone (ACTH), dehydroepiadrosterone (DHEA) and calculated free cortisol in healthy young women. Three-month administration of COC resulted in 1) significant increase of basal (454.0±125.0 to 860.9±179.7 nmol/l) and ACTH-stimulated serum cortisol in 30th min (652.3±60.5 to 1374.1±240.6 nmol/l); 2) no significant change of basal (15.4±7.3 to 18.9±8.5 nmol/l) and ACTH-stimulated salivary cortisol at the 30th min (32.4±8.8 to 32.9±9.0 nmol/l); 3) no significant change of basal serum cortisone (38,8±7.68 to 45.2±24.2 nmol/l) and ACTH-stimulated cortisone at the 30th (34.8±10.9 to 47.0±35.7 nmol/l); 4) significant increase of basal ACTH (17.2±9.0 to 38.2±29.4 ng/l), CBG (991.0±161.0 to 2332.0±428.0 nmol/l), and 5) no significant change of basal DHEA (24.6±15.7 to 22.6±11.7 μmol/l) and calculated basal value for free cortisol (22.8±14.9 to 19.2±6.9nmol/l). In conclusions, higher basal and ACTH-stimulated serum cortisol were found after three-month administration of COC, while basal and stimulated salivary cortisol were not significantly affected. Therefore, salivary cortisol can be used for assessment of adrenal function in women regularly using COC., K. Šimůnková, L. Stárka, M. Hill, L. Kříž, R. Hampl, K. Vondra., and Obsahuje bibliografii a bibliografické odkazy
This study aimed to examine relationships between DHEA(S), anthropometric parameters, oral glucose tolerance test derived data and lipid spectra in a Czech non-diabetic population. 380 healthy volunteers both with and without a family history of diabetes type 2 (DM2) were en rolled into the study (women: n=235, age 28.9±9.4 years, BMI 22.3±4.5 kg/m2, men: n=145, age 32.3±10.0 years, BMI 24.7±3.6 kg/m2). Spearman’s correlations (both without and with the adjustment for age, age and BMI), as well as ANCOVA were used. Non-adjusted data showed many “beneficial” correlations between DHEA(S) and both anthropometric and metabolic variables. Statistical analysis revealed that almost all correlations of DHEA(S) to adiposity and fat distribution in men as well as in women disappeared after the adjustment. There are, however, differences between men and women in the correlation of DHEA(S) to insulin sensitivity and lipid levels. The use of hormonal contraceptives (COC) is also an important factor in this relationship. In men and also in women using COC, DHEA-S after adjustment correlated positively with fasting and stimulated glucose, insulin and C-peptide, and negatively with insulin sensitivity. In this respect, the benefit of DHEA(S) supplementation seems - at least in terms of its alleged antiobesity and antidiabetogenic effects - to be more than controversial., B. Bendlová, J. Vrbíková, M. Hill, M. Vaňková, P. Lukášová, J. Včelák, D. Vejražková, K. Dvořáková, R. Hampl, K. Vondra, L. Stárka., and Obsahuje bibliografii a bibliografické odkazy
The ability to predict the success or failure of smoking cessation efforts will be useful for clinical practice. Stress response is regulated by two primary neuroendocrine systems. Salivary cortisol has been used as a marker for the hypothalamuspituitary- adrenocortical axis and salivary α-amylase as a marker for the sympathetic adrenomedullary system. We studied 62 chronic smokers (34 women and 28 men with an average age of 45.2±12.9 years). The levels of salivary cortisol and salivary α-amylase were measured during the period of active smoking, and 6 weeks and 24 weeks after quitting. We analyzed the men separately from the women. The men who were unsuccessful in cessation showed significantly higher levels of salivary α-amylase over the entire course of the cessation attempt. Before stopping smoking, salivary cortisol levels were higher among the men who were unsuccessful in smoking cessation. After quitting, there were no differences between this group and the men who were successful in cessation. In women we found no differences between groups of successful and unsuccessful ex-smokers during cessation. In conclusions, increased levels of salivary α-amylase before and during smoking cessation may predict failure to quit in men. On the other hand, no advantage was found in predicting the failure to quit in women. The results of our study support previously described gender differences in smoking cessation., M. Dušková ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
a1_Progesterone and estradiol are the foremost steroid hormones in human pregnancy. However, the origin of maternal progesterone has still not been satisfactorily explained, despite the generally accepted opinion that maternal LDL-cholesterol is a single substrate for placental synthesis of maternal progesterone. The question remains why the levels of progesterone are substantially higher in fetal as opposed to maternal blood. Hence, the role of the fetal zone of fetal adrenal (FZFA) in the synthesis of progesterone precursors was addressed. The FZFA may be directly regulated by placental CRH inducing an excessive production of sulfated 3β-hydroxy-5-ene steroids such as sulfates of dehydroepiandrosterone (DHEAS) and pregnenolone (PregS). Due to their excellent solubility in plasma these conjugates are easily transported in excessive amounts to the placenta for further conversion to the sex hormones. While the significance of C19 3β-hydroxy-5-ene steroid sulfates originating in FZFA for placental estrogen formation is mostly recognized, the question “Which maternal and/or fetal functions may be served by excessive production of PregS in the FZFA?“ - still remains open. Our hypothesis is that, besides the necessity to synthesize de novo all the maternal progesterone from cholesterol, it may be more convenient to utilize the fetal PregS. The activities of sulfatase and 3β-hydroxysteroid dehydrogenase (3β-HSD) are substantially higher than the activity of cytochrome P450scc, which is rate-limiting for the placental progesterone synthesis from LDL-cholesterol. However, as in the case of progesterone synthesis from maternal LDL-cholesterol, the relative independence of progesterone levels on FZFA activity may be a consequence of substrate saturation of enzymes converting PregS to progesterone., a2_Some of the literature along with our current data (showing no correlation between fetal and maternal progesterone but significant partial correlations between fetal and maternal 20α-dihydroprogesterone (Prog20α) and between Prog20α and progesterone within the maternal blood) indicate that the localization of individual types of 17β-hydroxysteroid dehydrogenase is responsible for a higher proportion of estrone and progesterone in the fetus, but also a higher proportion of estradiol and Prog20α in maternal blood. Type 2 17β-hydroxysteroid dehydrogenase (17HSD2), which oxidizes estradiol to estrone and Prog20α to progesterone, is highly expressed in placental endothelial cells lining the fetal compartment. Alternatively, syncytium, which is directly in contact with maternal blood, produces high amounts of estradiol and Prog20α due to the effects of type 1, 5 and 7 17β-hydroxysteroid dehydrogenases (17HSD1, 17HSD5, and 17HSD7, respectively). The proposed mechanisms may serve the following functions: 1) providing substances which may influence the placental production of progesterone and synthesis of neuroprotective steroids in the fetus; and 2) creating hormonal milieu enabling control of the onset of labor., M. Hill ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
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
Elevated levels of glucocorticoids lead to the development of obesity and metabolic syndrome. Local glucocorticoid levels are regulated through the enzyme 11 β -hydroxysteroid dehydrogenase 1 (11 β -HSD 1), an enzyme that regenerates active cortisol from inert cortis one. Increased expression of 11 β - HSD 1 in adipose tissue promotes higher body mass index (BMI), insulin resistance, hypertension, and dyslipidemia. Human 11 β - HSD 1 is also responsible for inter-conversion of 7-hydroxylate metabolites of dehydroepiandrosterone (7-OH-DHEA) to their 7-oxo-form. To better understanding the mechanism of the action, we focused on 7-OH- and 7-ox o-DHEA, and their circulating levels during the reductive treatment in adolescent obese patients. We determined plasma levels of 7 α -OH-DHEA, 7 β -OH- DHEA, and 7-oxo-DHEA in 55 adolescent patients aged 13.04- 15.67 years, BMI greater than 90 th percentile. Samples were collected before and after one month of reductive therapy. Circulating levels of 7 α -OH-DHEA decreased during the reductive therapy from 1.727 (1.614; 1.854 , transformed mean with 95 % confidence interval) to 1.530 nm ol/l (1.435; 1.637, p<0.05) in girls and from 1.704 (1.583; 1. 842) to 1.540 nmol/l (1.435; 1.659, p<0.05) in boys. With regard to the level of 7-oxo-DHEA, a significant reduction from 1. 132 (1.044; 1.231) to 0.918 nmol/l (0.844; 1.000, p<0.05) was found after the treatment, but only in boys. No significant difference in 7 β -OH-DHEA levels was observed. In conclusions, diminished levels of 7 α -OH-DHEA indicate its possible effect on activity of 11 β -HSD 1. Further studies are necessary to clarify whether competitive substrates for 11 β -HSD 1 such as 7 α -OH-DHEA could inhibit production of glucocorticoids and may be involved in metabolic processes leading to reduction of obesity., L. Máčová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Steroids are important marker s in pregnancy. Although estimating their levels separately in umbilical arterial (UA) and venous blood (UV) enable more precise insights into the functioning fetoplacental unit compared to using mixed umbilical blood (UM), selective aspiration of UA and UV is technically more demanding than collecting UM. We measured the levels of 67 unconjugated steroids and steroid polar conjugates in UA and UV using GC-MS in 80 women giving birth within weeks 28 to 42 of gestation. The samples were sorted into three groups: women entering labor within weeks 28- 32 (group A, n=19), weeks 33-37 (group B, n=19), and weeks 38-42 (group C, n=42) of gestation, respectively. The preterm labo rs were due to pathologies unrelated to steroid status. Most unconjugated steroids exhibited pronounced arteriovenous differences (AVD). The AVD were less distinct in more stable steroid conjugates. Most steroids positively correlate with gestational age, but unconjugated 5 β -reduced pregnanes show negative correlations, as do testosterone and androstenediol, substrates for the placental synthesis of estrogens. Tight correlations be tween steroids in UA and UV indicate that steroid measurements in UA, UV and UM can be accurately derived from each other, which is important for the diagnostics of steroid related diseases in newborns., A. Pašková ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy