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Biomedical subjects

L Stárka

Publications and source records attributed to L Stárka.

At least 19 recordsLinked to original sources

Salivary cortisol in low dose (1 microg) ACTH test in healthy women: comparison with serum cortisol.

To date, a single report has appeared on the use of salivary cortisol for adrenal function testing with a low dose ACTH, although 1 microg has become preferred as a more physiological stimulus than the commonly used 250 microg ACTH test. Our present study was aimed to obtain physiological data on changes of free salivary cortisol after 1 microg 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 microg 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.

Adrenal Glands↗

Hormonal homeostasis in a group of 216 aging Czech males and correlation with responses to a questionnaire of the University of St Louis.

UNLABELLED: The male aging process is accompanied by changes in the levels of several types of hormones. Falling levels of androgenic-anabolic steroids (total testosterone, free testosterone, biologically accessible testosterone, dehydroepiandrosterone) correspond to a group of symptoms referred to as PADAM syndrome (Partial Androgen Deficiency in the Aging Male). In the case of those carefully examined patients with symptoms of PADAM and proven hypogonadism, administering androgen supplements can alleviate some of the undesirable manifestations. In its literature, the University of St Louis repeatedly refers to its questionnaire as a verbal tool for the detection of possible hypogonadism. The aim of this study was to ascertain to what extent the aging process is evident in hormonal homeostasis detected in laboratory testing, and the extent to which this data is in accord with the evaluation of responses to questions in the University of St Louis questionnaire. METHOD: 216 men aged over 50 years were examined. Measurements were taken of: testosterone; the index of free testosterone; androstenedione; dihydrotestosterone; dehydroepiandrosterone and its sulfate; isomers 7alpha- and 7beta-hydroxydehydroepiandrosterone; epitestosterone; luteinizing hormone (LH); follicle-stimulating hormone (FSH); prolactin; and sexual hormone-binding globulin (SHBG). Evaluations of the patients' responses to the University of St Louis questionnaire were compared with the results of the laboratory tests. RESULTS: The study confirms that the most prominent phenomenon is that of an age-related decrease in the index of free testosterone, which is indicated in particular by an increase in the level of SHBG, and by a decrease in dehydroepiandrosterone and its derivatives. No significant correlation was found between levels of hormones and single items on the questionnaire, nor with the overall score arrived at by studying the patients' data.

Aged↗

The existence of a male equivalent of the polycystic ovary syndrome--the present state of the issue.

The polycystic ovary syndrome (PCOS) in women belongs to the most frequent endocrinopathies. This syndrome is characteristic by a hormonal and metabolic imbalance. It seems to be a kind of an oligogenic disease resulting from the interaction among several key genes and environmental effects. Considering the genetic basis of this syndrome there is no reason why the syndrome could not occur in men as well, be it with a different symptomatic expression. Premature baldness before the age of thirty used to be suggested as a symptom of the male PCOS equivalent. Yet there still seems to be rather a meagre attention devoted to the endocrinological changes in men in the specialised literature, although there do exist genealogical studies on the occurrence of alopecia or glucose metabolic disorder in male members of the families where a considerable number of females were affected by PCOS.

Alopecia↗

[Metamorphosis of endocrinology].

During the last half of century we witnessed not only changes in the definition of hormone, in the conception of endocrinology and in understanding of mechanisms of hormone action, but also an immense development of technical tools of endocrine diagnostic and therapy. Endocrinology has had a profound impact on other branches of medicine with the consequence that the frontiers of classical endocrinology are slowly vanishing. It is time to ask what will be the future demands of patients and whether there will be appropriate number of specialists in endocrinology in the near future. Besides the present type of care of the patients with endocrinopathies it is necessary to envision a new type of patient requesting "comfort therapy", as e.g. improvement of signs of aging, declining sexuality, or body height or weight.

Endocrinology↗

[Testosterone treatment of sarcopenia].

Testosterone increases muscle mass and decreases fat mass by mechanism including androgen receptors. Testosterone induces skeletal muscle fibre hypertrophy and increases the number of satellite cells. It also promotes the differentiation of mesenchymal multipotent cells into myogenic lineage and inhibits their differentiation into the adipogenic lineage. Meta-analyses of clinical trials provide evidence that testosterone treatment, depending on dose, increases the skeletal muscle mass and to some degree also muscle strength. The most frequent adverse effects of testosterone treatment in aging men are an increase of hematocrit and increased risk of prostate events.

Humans↗

Circulating neuroactive C21- and C19-steroids in young men before and after ejaculation.

Twelve neuroactive and neuroprotective steroids, androgens and androgen precursors i.e. 3alpha,17beta-dihydroxy-5alpha-androstane, 3alpha-hydroxy-5alpha-androstan-17-one, 3alpha-hydroxy-5beta-androstan-17-one, androst-5-ene-3beta,17beta-diol, 3beta,17alpha-dihydroxy-pregn-5-en-20-one (17alpha-hydroxy-pregnenolone), 3beta-hydroxy-androst-5-en-17-one (dehydroepiandrosterone, DHEA), testosterone, androst-4-ene-3,17-dione (androstenedione), 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone), 3beta-hydroxy-pregn-5-en-20-one (pregnenolone), 7alpha-hydroxy-DHEA, and 7beta-hydroxy-DHEA were measured using the GC-MS system in young men before and after ejaculation provoked by masturbation. The circulating level of 17alpha-hydroxypregnenolone increased significantly, whereas the other circulating steroids were not changed at all. This fact speaks against the hypothesis that a drop in the level of neuroactive steroids, e.g. allopregnanolone may trigger the orgasm-related increase of oxytocin, reported by other authors.

17-alpha-Hydroxypregnenolone↗

Steroids and thermogenesis.

Apart from thyroid hormones, as the main hormonal regulators of obligatory thermogenesis, and catecholamines, as major hormonal regulators of facultative thermogenesis, production of heat in homeotherms can also be influenced by steroids. Generally, hormones can influence heat production by regulating the activity of various enzymes of oxidative metabolism, by modulating membrane protein carriers and other membrane or nuclear protein factors. Proton carriers in the inner mitochondrial membrane, known as uncoupling proteins, play the key role in heat dissipation to the detriment of the formation of energy-rich phosphates. In this minireview we have focused on the effects of steroids and thyroid hormones on heat production in brown adipose tissues and in skeletal muscles, with particular respect to their effect on uncoupling protein expression. Apart from hormonal steroids, dehydroepiandrosterone, an important precursor in the metabolic pathway leading to hormonal steroids which possess many, mostly beneficial effects on human health, modulates metabolic pathways which may lead to increased heat production. Recent studies demonstrate that 7-oxo-dehydroepiandrosterone, one of its 7-oxygenated metabolites, is even more effective than dehydroepiandrosterone. Recent findings of various actions of these steroids support the view that they may also participate in modulating thermogenic effects.

Adrenal Cortex Hormones↗

The computer modelling of human TRH receptor, TRH and TRH-like peptides.

The aim of this work was to verify the possibility of interactions between the human TRH receptor (an integral membrane protein which belongs to family 1 of G-protein coupled receptors) and TRH-like peptides presented in the prostate gland. These peptides are characterized by substitution of basic amino acid histidine (related to authentic TRH) for neutral or acidic amino acid, such as glutamic acid, phenylalanine, glutamine or tyrosine. The physiological function of TRH-like peptides in peripheral tissues is not precisely known. However, according to our recent experiments, we assume the existence of a local hormonal network formed by TRH-like peptides and TSH in the prostate gland. The network can be associated with circulating thyroid and steroid hormones, and may represent a new regulatory mechanism influencing the proliferative ability of prostatic tissue. A similar network of authentic TRH and TSH was already found in the gastrointestinal tract. The experimentally determined 3D-structures of human TRH receptor (hTRHr) and TRH-like peptides are not available. From this point of view we used de novo modeling procedures of G-protein coupled receptors on an automated protein modeling server used at the Glaxo Wellcome Experimental Research (Geneva, Switzerland). 3D-structures of TRH-like peptides were determined with a computer program CORINA (written by the team of J. Gasteiger, Computer-Chemie-Centrum and Institute for Organic Chemistry, University of Erlangen-Nurenberg, Germany). The generated PDB files with 3D-coordinates were visualized with Swiss-Pdb Viewer Release 3.51 (Glaxo Wellcome). From recent results it is evident that polar amino acids belonging to the extracellular terminus of hTRHr transmembrane regions can participate in interactions between TRH and hTRHr. There is no direct evidence that TRH-like peptides interact with the presented hTRHr model. On the contrary, with respect to the similar 3D-shape and the identity of terminal amino acids, it appears that these interactions are highly probable as well as the nearly 100 % cross-reactions between TRH or TRH-like peptides and antibody specific against authentic TRH. Closed terminal amino acids (pyroglutamic acid and proline-amide) of TRH or TRH-like peptides are important for these interactions. Desamido-TRH or glutamyl metabolites will be repelled by the negative potential of ASP195 (E: D93) and GLU298 (G: E137).

Amino Acid Sequence↗

Flutamide suppresses adrenal steroidogenesis but has no effect on insulin resistance and secretion and lipid levels in overweight women with polycystic ovary syndrome.

The authors evaluate the effects of 2 months of treatment with 250 mg flutamide daily on adrenal steroidogenesis (ACTH test) and metabolic parameters (lipids, insulin resistance) in 12 PCOS women aged 33.8 +/- 7.5 years and with a BMI of 33.6 +/- 4.2 kg/m2. Significant decreases in basal DHEA-S (p < 0.0001), DHEA (p < 0.01) and androstenedione (p < 0.05), in the ACTH-stimulated levels of DHEA-S (p < 0.0001), testosterone (p < 0.05) and in ACTH-stimulated 17beta-hydroxysteroid dehydrogenase activity (p < 0.01) were observed. No significant change in basal blood glucose, insulin, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides or in insulin resistance, as estimated by the insulin tolerance test, was found. Flutamide is effective in reducing adrenal androgen production in overweight women, but has no effect on lipid spectrum or on insulin resistance.

17-Hydroxysteroid Dehydrogenases↗

Hormonal profile of men with premature balding.

OBJECTIVE: Premature androgenic alopecia has been suggested as a feature of the male equivalent of the syndrome of polycystic ovary. However, the hormonal pattern of men with premature balding has been investigated in only a few studies with inconsistent results. MATERIAL AND METHODS: We examined 37 men with premature balding (defined as frontoparietal and vertex hair loss before the age of 30 years with alopecia defined as grade 3 vertex or more on the alopecia classification scale of Hamilton with Norwood modification). The plasma concentrations of total testosterone, dihydrotestosterone, epitestosterone, androstenedione, cortisol, 17-OH-progesterone (17OHP), estradiol, LH, FSH, prolactin, SHBG and TSH and free thyroxine were measured. RESULTS: The frequency of subnormal values in SHBG, FSH, testosterone and epitestosterone (but not in free androgen index) was significant in the balding men. A borderline significant trend was recorded with respect to increased levels in 17OH-P and prolactin. CONCLUSIONS: The hormonal pattern of a substantial number of men with premature balding resembles in some respects the hormonal pattern of women with polycystic ovary syndrome.

Adult↗

Metabolic and endocrine effects of treatment with peroral or transdermal oestrogens in conjunction with peroral cyproterone acetate in women with polycystic ovary syndrome.

OBJECTIVE: To compare the influence of transdermal and peroral oestrogen treatments in conjunction with cyproterone acetate (CPA) on metabolic and hormonal parameters in women with polycystic ovary syndrome (PCOS). PATIENTS AND METHODS: Twenty-four women with PCOS, aged 25.4+/-4.3 (mean+/-s.d.) years, body mass index 24.5+/-3.9 kg/m2 were randomly assigned to receive either transdermal oestradiol plus CPA (n=12) or a peroral oestradiol-CPA combination (n=12). Before and after 3 months of treatment, basal blood samples, euglycaemic hyperinsulinaemic clamp combined with indirect calorimetry and arginine tests were performed. ANOVA and Student's t-test or Wilcoxon's test were used for statistical analyses. RESULTS: After peroral oestradiol-CPA, insulin sensitivity (P<0.004) and the disposition index as the function of insulin sensitivity and secretion (P<0.0001) decreased significantly. Fasting insulin (P<0.05), cholesterol (P<0.05), high-density lipoprotein cholesterol (P<0.05) and sex-hormone binding globulin (P<0.0001) increased significantly. Dehydroepiandrosterone (P<0.05) and 17-OH progesterone (P<0.01) decreased significantly. After transdermal oestradiol+CPA, no significant changes were observed in sex-hormone binding globulin and androgen concentrations, insulin sensitivity or disposition index. CONCLUSIONS: In women with PCOS, peroral oestrogens (at doses common in combined oral contraceptives) led to a significant impairment in insulin secretion and action. In contrast, the transdermal application of oestrogens did not significantly influence insulin sensitivity.

Administration, Cutaneous↗

What may be the markers of the male equivalent of polycystic ovary syndrome?

Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women (with a prevalence of 5-10 %), is characterized by hormonal and metabolic imbalance. Complexity of symptoms of close relatives of women with PCOS and genetic autosomal trait initiated a hypothesis about the existence of a male equivalent of PCOS. Premature alopecia was suggested as one of the signs of a male phenotype of this syndrome. The present study investigated a group of 30 men, in which premature hair loss started before 30 years of age. In all patients, their hormonal profile was determined. It was possible to form two subgroups. The first one showed similar hormonal changes as women with PCOS, the other had either no anomalies in steroid spectrum or just only lower level of sexual hormones binding globulin (SHBG). Both subgroups did not differ in either BMI or age. In all men with premature alopecia insulin tolerance test was also carried out and the occurrence of allele 3 INS VNTR was investigated, which is one of the candidate genes for PCOS. The subgroup with hormonal changes resembling those of women with PCOS showed a significantly higher insulin resistance than the group without these changes. About one third of the premature balding men showed the combination of hormonal shifts and higher insulin resistance. This frequency corresponds to the prevalence of PCOS in women. There was no significant difference between the two subgroups in the occurrence of allele 3 INS VNTR.

Adolescent↗

Epitestosterone.

Epitestosterone has been identified as a natural component of biological fluids of several mammals including man. For a long time it was believed that it is a metabolite without any hormonal activity and without any marked relationship to the hormonal state in health and disease. Neither the biosynthetic pathway nor the site of its formation in man have been unequivocally confirmed to date. It apparently parallels the formation of testosterone (T), but on the other hand its concentration is not influenced by exogenous administration of testosterone. This fact creates the basis of the present doping control of testosterone abuse. In 1989 an observation was presented in a dermatological study that epitestosterone exerts an effect counteracting the action of testosterone on flank organ of Syrian hamster. Further studies showed that a complex action consisting of competitive binding of epitestosterone to androgen receptor, of inhibition of testosterone biosynthesis and its reduction to dihydrotestosterone and of antigonadotropic activity could be demonstrated in rat, mice and human tissues. It can be presumed that epitestosterone as a natural hormone can contribute to the regulation of such androgen dependent events as, e.g. the control of prostate growth or body hair distribution.

Androgen Antagonists↗

Cardiovascular risk factors in young Czech females with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) could be associated with a variety of signs of metabolic syndrome. The aim of our study was to compare the cardiovascular risk factors in PCOS women and in a control group selected from a random population sample. METHODS AND RESULTS: 50 PCOS women with a mean (+/-SD) age of 30.7 +/- 4.2 years, and 335 controls with a mean age of 29.9 +/- 3.1 years selected from a random population sample of nine districts of the Czech Republic were compared for basic anthropometric characteristics, blood pressure, plasma lipids and fasting glucose. PCOS women had a significantly higher body mass index (BMI). After adjusting for BMI, PCOS women had higher blood pressure and LDL-cholesterol, and lower HDL and HDL-cholesterol/total ratio. Arterial hypertension was more prevalent in PCOS women than in controls. There was no difference in the prevalence of impaired fasting glucose between both groups. Impaired glucose tolerance was found in 11.8% of PCOS women. Diabetes mellitus was more frequent in PCOS families. CONCLUSIONS: Czech PCOS women, even in their thirties, show a significantly worse cardiovascular risk profile than a control group selected from a random population sample. The differences cannot be explained by obesity.

Adult↗

Pregnanolone isomers, pregnenolone and their polar conjugates around parturition.

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 (3beta-hydroxy-5beta-pregnan-20-one) in both maternal and umbilical plasma was much lower than that of other pregnanolone isomers. The levels of 3beta-hydroxy-pregnanolone isomers were significantly higher in the umbilical plasma than in the maternal, while the differences in 3alpha-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 3alpha/3beta-isomers and 5alpha/5beta-isomers around parturition. The possible physiological consequences of the findings are indicated.

Female↗

[Hormones and quality of life in aging men].

BACKGROUND: Aging men suffer from a decrease of androgen-anabolic steroids known as "Partial Androgen Decline in the Aging Male" (PADAM) that is sometimes compensated by the use of androgen replacement therapy. METHODS AND RESULTS: To decide whether androgen therapy should be considered, hormonal serum levels are commonly tested. In addition, the St. Louis questionnaire is used as and indication. Accordingly, serum levels of testosterone, androstendione, dihydrotestosterone, dehydroepiandrosterone, its sulphate, epimers of 7-hydroxy-dehydroepiandrosterone, epitestosterone, lutropin, follitropin, prolactin and sex hormone binding globulin were measured in 216 men over 50 years of age. Further, the Sr. Louis questionnaire was applied and the extent of the relations among the data was evaluated. RIA and IRMA kits from Immunotech and Orion-Diagnostica were used for measurement of the hormones except epitestosterone and 7-hydroxy-dehydroepiandrosterone epimers, which were determined using specific radioimmunoassays. CONCLUSIONS: The decline in the index of free testosterone, given by the increase of SHBG levels, as well as the decrease in the levels of DHEA and its derivates were the most prominent. No correlation was found between the levels of hormones and the individual items of the questionnaire or with the total score calculated from the questionnaire data. In conclusion, the University of Saint Louis questionnaire did not give a reliable indication of an androgen deficit. However, the found values and their changes can still be helpful during the decision process concerning indication and initiation of hormone replacement.

Aged↗

Dehydroepiandrosterone - is the fountain of youth drying out?

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.

Aged↗

[Metformin has a positive effect on disorders of carbohydrate metabolism in long-term care with low doses of prednisone].

BACKGROUND: The influence of long-term, low doses of prednison administration (< 0.3 mg/kg/day) on glucoregulation and glucose tolerance was studied in 20 female patients (15-20 yrs), including verification of possibility to correct the impairment of glucose tolerance (IGT) by metformin (M). METHODS AND RESULTS: During prednison treatment, we found typical signs of insulin resistance manifestation: HOMAIR 3.55 (5.13), blood insulin/glucose ratio 3.8 (5.84), QUICKI 0.61 (0.124). These were associated with higher Langerhans (L.) islets hormone secretion detected under basal conditions as well as after bolus of 5 g arginine chloride. However, detailed analysis of hormone secretion ratios revealed distinct signs of L. islets function impairment and subcompensation. Specifically, low ratio C peptide/proinsulin and C peptide/glucagon were characteristicaly observed. Six months of M. administration (1000 mg/day) had a beneficial effect on glucose metabolisms deviations as indicated by the following: insulin resistance decreased (HOMAIR 1.96 (1.60), insulin/glucose ratio 2.34 (1.52), QUICKI increased at 0.699 (0.238)). At the same time we found a decrease in the basal levels of insulin, proinsulin, glucagon, C peptide and amyline, and AUC proinsulin and glucagon as well. HOMAsecretion decreased from an initial value of 389 (376) to 207 (119). CONCLUSIONS: Judging by the new hormonal secretion ratios, the L. islets' function following M. treatment substantially improved. From the clinical point of view, it is important to note that M. was tolerated very well. No patient interrupted the follow up because of M. intolerance. IGT in the whole group normalised, in spite of the fact that no accent was put on the regime, diet including. The 90% of lactate values did not exceed 1.7 mmol/l. Based on the results, we may conclude that M. has a beneficial effect on long-term, low doses of glucocorticoid-related (induced) glucose metabolism impairment, and therefore, M. administration could be recommended, particularly in the situations with higher levels of glycosylated hemoglobin.

Adolescent↗