The LRP5 gene is believed to be primarily associated with bone metabolism via Wnt signaling. The latter pathway, however, appears to control various other systems outside the skeleton. To find the relationships of the LRP5 gene to serum follicle stimulating hormone (FSH ) and luteinizing hormone (LH) in the cohort of normal postmenopausal women, we identified the C/T (c.4037:A1330V) polymorphism in the LRP5 gene using a restriction analysis of the PCR product in a cohort of 165 untreated pre- and post-menopausal women. In a subset of 111 post-menopausal women we analyzed the association between the LRP5 genotype and serum levels of sex-hormones including FSH and LH. The distribution of CC, TC and TT genotypes of the C/T polymorphism in the whole group was 73.9 %, 23.6 % and 2.4 %, respectively, which is comparable with other Caucasian populations. As no TT homozygote was found in the group of post-menopausal women, serum sex-hormones were compared between CC and TC genotypes. Women with the CT allele combination had markedly higher serum FSH levels as compared to carriers of the CC genotype (p<0.004). No differences between these genotypes were found in serum LH levels as well as the circulating sex-steroids such as estradiol, testosterone, dehydroepiandrosterone and/or its sulphate, androstenedione and SHBG. To conclude, the LRP5 gene is associated with circulating FSH in normal post-menopausal women in the present study. The mediating role of subtle undetectable variations in estrogen levels is discussed. We did not find any relationship between the LRP-5 genotype and serum LH levels., I. Žofková, M. Hill, K. Zajíčková., and Obsahuje bibliografii a bibliografické odkazy
Experimental and epidemiological studies suggest that calcium intake is inversely related to weight gain. Calcium of dairy origin has been shown to be more effective in promoting weight loss. However, clinical studies yielded controversial results concerning the role of calcium intake in weight change. The aim of this study was to ascertain whether the addition of calcium can affect the outcome of 3-week weight management (WM) with a hypocaloric diet characterized by a decreased calcium intake. Overweight/obese women (n=67; BMI 32.2±4.1 kg/m2; age 49.1±12.1 years) underwent a 4-week comprehensive WM program. WM included a 7 MJ/day diet resulting in a stable weight during the first week and a 4.5 MJ/day diet with mean daily calcium intake 350 mg during the second to fourth week. Participants were divided into three age- and BMI-matched groups who received placebo or calcium (500 mg/day). Calcium was administered either as carbonate or calcium of dairy origin (Lactoval). There was no significant difference in weight loss in response to WM between the placebo-treated and calcium-treated groups. However, addition of calcium to the diet resulted in a lower hunger score in the Eating Inventory as well as a decrease in plasma resistin levels. Body composition measured by bioimpedance demonstrated that added calcium leads to preservation of fat-free mass. Nevertheless, a greater loss of fat-free mass in the placebo group might be partly due to a greater loss of water., K. Kabrnová-Hlavatá, V. Hainer, M. Gojová, P. Hlavatý, V. Kopský, J. Nedvídková, M. Kunešová, J. Pařízková, M. Wagenknecht, M. Hill, J. Drbohlav., and Obsahuje bibliografii a bibliografické odkazy
Obesity in children is accompanied by increased circulating leptin concentrations. Girls have higher leptin concentrations than boys. The aim of our study was to compare serum leptin levels before and after a five-week weight reduction program and to study the relationship of leptin levels, serum total cholesterol, and androgens (testosterone, dehydroepiandrosterone, dehydroepiandrosterone sulphate) in 33 obese boys (age: 12.71.97 years, BMI: 30.46±4.54) and 66 obese girls (age: 12.7±2.51 years, BMI: 29.31±4.62). We found that serum leptin concentrations in obese children were significantly decreased after a weight reduction program (before 20.79±9.61 ng/ml, after 13.50±8.65 ng/ml in girls; before 12.25±10.09 ng/ml and after 5.18±3.56 ng/ml in boys, p<0.0001 in both genders). Leptin levels correlated positively with the body mass index before and after weight reduction. There was a positive association in obese boys and a negative one in obese girls between leptin levels and the WHR (waist to hip circumference ratio). Serum leptin also shows a strong relationship to fat distribution (p = 0.02 in boys, p<0.0001 in girls). No significant correlation was found between leptin concentrations and total cholesterol or androgens. We confirmed that leptin is a sensitive parameter of body composition and weight reduction in obese children., R. Pilcová, J. Šulcová, M. Hill, P. Bláha, L. Lisá., and Obsahuje bibliografii
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
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
The levels of four pregnanolone isomers and their polar conjugates and pregnenolone sulfate were measured in the plasma of 13 and 7 women at delivery with subarachnoidal and epidural analgesia, respectively, and in corresponding samples of umbilical plasma using a simple quadrupole GC/MS system with electron impact ionization (pregnenolone isomers), RIA following HPLC separation (pregnenolone) and specific RIA (pregnanolone sulfate). The concentration of epipregnanolone (3b-hydroxy-5b-pregnan-20-one) in both maternal and umbilical plasma was much lower than that of other pregnanolone isomers. The levels of 3b-hydroxy-pregnanolone isomers were significantly higher in the umbilical plasma than in the maternal, while the differences in 3a-hydroxy-isomers were insignificant. The differences in conjugates were insignificant with the exception of allopregnanolone, the levels of which were lower in umbilical plasma. In all the pregnanolone isomers, a significantly lower conjugated/unconjugated steroid ratio was found in the umbilical plasma than in the maternal plasma. In addition, time profiles of the steroids were measured around parturition and in the postpartum period in the maternal serum. Similarly, the levels of polar conjugates of all pregnanolone isomers were followed during parturition. Changes in concentrations of free steroids exhibited a similar pattern, with a fall primarily within the first hour after delivery. The decrease in conjugated steroids was shifted to the interval within the first hour and first day after delivery, and the changes were more pronounced. The time profiles of the conjugated/free steroid ratio exhibited a significant decrease within the first hour and the first day after delivery in all of the isomers investigated. A decrease was also observed in the ratio of 3a/3b- isomers and 5a/5b- isomers around parturition.The possible physiological consequences of the findings are indicated., J. Klak, M. Hill, A. Pařízek, H. Havlíková, M. Bičíková, R. Hampl T. Fait, J. Šulcová V. Pouzar, R. Kancheva, L. Stárka., and Obsahuje bibliografii
In this review, we focused on the intersection between steroid metabolomics, obstetrics and steroid neurophysiology to give a comprehensive insight into the role of sex hormones and neuroactive steroids (NAS) in the mechanism controlling pregnancy sustaining. The data in the literature including our studies show that there is a complex mechanism providing synthesis of either pregnancy sust aining or parturition provoking steroids. This mechanism includes the boosting placental synthesis of CRH with approaching parturition inducing the excessive synthesis of 3β-hydroxy-5-ene steroid sulfates serving primarily as precursors for placental synthesis of progestogens, estrogens and NAS. The distribution and changing activities of placental oxidoreductases are responsible for the activation or inactivation of the aforementioned steroids, which is compartment-specific (maternal and fetal compartments) and dependent on gestational age, with a tendency to shift the production from the pregnancy-sustaining steroids to the parturition provoking ones with an increasing gestational age. The fetal and maternal livers catabolize part of the bioactive steroids and also convert some precursors to bioactive steroids. Besides the progesterone, a variety of its 5α/β-reduced metabolites may significantly influence the maintenance of human pregnancy, provide protection against excitotoxicity following acute hypoxic stress, and might also affect the pain perception in mother and fetus. and M. Hill ... [et al.].
To date, a single report has appeared on the use of salivary cortisol for adrenal function testing with a low dose ACTH, although 1 μg has become preferred as a more physiological stimulus than the commonly used 250 μg ACTH test. Our present study was aimed to obtain physiological data on changes of free salivary cortisol after 1 μg ACTH stimulation. This approach was compared with the common method based on the changes of total serum cortisol. Intravenous, low-dose ACTH test was performed in 15 healthy women (aged 22-40 years) with normal body weight, not using hormonal contraceptives, in the follicular phase of the menstrual cycle. Blood and saliva for determination of cortisol were collected before ACTH administration and 30 and 60 min after ACTH administration. Basal concentration of salivary cortisol (mean ± S.E.M., 15.9±1.96 nmol/l) increased after 1 μg ACTH to 29.1±2.01 nmol/l after 30 min, and to 27.4±2.15 nmol/l after 60 min. The differences between basal and stimulated values were highly significant (p<0.0001). The values of salivary cortisol displayed very little interindividual variability (p<0.04) in contrast to total serum cortisol values (p<0.0001) A comparison of areas under the curve (AUC) related to initial values indicated significantly higher AUC values for salivary cortisol than for total serum cortisol (1.89±0.88 vs. 1.22±0.19, p<0.01). Correlation analysis of serum and salivary cortisol levels showed a borderline relationship between basal levels (r=0.5183, p=0.0525); correlations after stimulation were not significant. Low-dose ACTH administration appeared as a sufficient stimulus for increasing salivary cortisol to a range considered as a normal adrenal functional reserve., K. Šimůnková, R. Hampl, M. Hill, J. Doucha, L. Stárka, K. Vondra., and Obsahuje bibliografii a bibliografické odkazy