Vitamin D and new insights into pathophysiology of type 2 diabetes.

Deficiency in vitamin D plays a role in the onset and development of insulin resistance (IR) and type 2 diabetes (T2DM). A normal level of vitamin D is able to reduce low grade inflammation, which is a major process in inducing insulin resistance. It is also engaged in maintaining low resting levels of reactive species and radicals, normal Ca2+ signaling, a low expression of pro-inflammatory cytokines but increased formation of anti-inflammatory cytokines. Vitamin D is also able to prevent hypermethylation (of DNA) and consequent functional inactivation of many genes, as well as other epigenetic alterations in ß cells and in other insulin-sensitive peripheral tissues, mainly liver, adipose tissue and muscle. Vitamin D deficiency thus belongs to key factors accelerating the development of IR and consequently T2DM as well. However, vitamin D supplementation aimed at the control of glucose homeostasis in humans showed controversial effects. As a result, further studies are running to gain more detailed data needed for the full clinical utilization of vitamin D supplementation in the prevention and treatment of T2DM. Until new results are published, supplementation with high doses of vitamin D deficiency is not recommended. However, prevention of vitamin D deficiency and its correction are highly desired.

Determination of Intraprostatic and Intratesticular Androgens.

Androgens represent the main hormones responsible for maintaining hormonal balance and function in the prostate and testis. As they are involved in prostate and testicular carcinogenesis, more detailed information of their active concentration at the site of action is required. Since the introduction of the term intracrinology as the local formation of active steroid hormones from inactive precursors of the adrenal gland, mainly dehydroepiandrosterone (DHEA) and DHEA-S, it is evident that blood circulating levels of sex steroid hormones need not reflect their actual concentrations in the tissue. Here, we review and critically evaluate available methods for the analysis of human intraprostatic and intratesticular steroid concentrations. Since analytical approaches have much in common in both tissues, we discuss them together. Preanalytical steps, including various techniques for separation of the analytes, are compared, followed by the end-point measurement. Advantages and disadvantages of chromatography-mass spectrometry (LC-MS, GC-MS), immunoanalytical methods (IA), and hybrid (LC-IA) are discussed. Finally, the clinical information value of the determined steroid hormones is evaluated concerning differentiating between patients with cancer or benign hyperplasia and between patients with different degrees of infertility. Adrenal-derived 11-oxygenated androgens are mentioned as perspective prognostic markers for these purposes.

Exposure to bisphenols and parabens during pregnancy and relations to steroid changes.

BACKGROUND: The harmful effects of endocrine disrupting compounds (EDCs) on human health are generally well-known, and exposure during fetal development may have lasting effects. Fetal exposure to bisphenol A (BPA) has been recently relatively well-studied; however, less is known about alternatives such as bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF), which have started to appear in consumer products. Parabens are another widespread group of EDCs, with confirmed transplacental passage. The usage of many cosmetic, pharmaceutical and consumer products during the pregnancy that may contain parabens and bisphenols has led to the need for investigation. OBJECTIVES: To shed more light into the transplacental transport of BPA, its alternatives, and parabens, and to study their relation to fetal steroidogenesis. METHODS: BPA, BPS, BPF, BPAF, methylparaben, ethylparaben, propylparaben, butylparaben, benzylparaben and 15 steroids including estrogens, corticoids, androgens and immunomodulatory ones were determined in 27 maternal (37th week of pregnancy) and cord plasma samples using liquid chromatography - tandem mass spectrometry methods. RESULTS: In cord blood, significantly higher BPA levels (p=0.0455) were observed compared to maternal plasma. The results from multiple regression models showed that in cord blood, methylparaben (ß=-0.027, p=0.027), propylparaben (ß=-0.025, p=0.03) and the sum of all measured parabens (ß=-0.037, p=0.015) were inversely associated with testosterone levels. CONCLUSION: To the best of our knowledge, this is the first study reporting the simultaneous detection of BPA, alternative bisphenols, parabens and steroids in maternal and cord plasma. Our study confirmed the transplacental transport of BPA, with likely accumulation in the fetal compartment. The negative association of cord blood parabens and testosterone levels points to possible risks with respect to importance of testosterone for prenatal male development.

Occurrence and reproductive roles of hormones in seminal plasma.

Only 2-5% of seminal fluid is composed of spermatozoa, while the rest is seminal plasma. The seminal plasma is a rich cocktail of organic and inorganic compounds including hormones, serving as a source of nutrients for sperm development and maturation, protecting them from infection and enabling them to overcome the immunological and chemical environment of the female reproductive tract. In this review, a survey of the hormones found in human seminal plasma, with particular emphasis on reproductive hormones is provided. Their participation in fertilization is discussed including their indispensable role in ovum fertilization. The origin of individual hormones found in seminal plasma is discussed, along with differences in the concentrations in seminal plasma and blood plasma. A part of review is devoted to methods of measurement, emphasising particular instances in which they differ from measurement in blood plasma. These methods include separation techniques, overcoming the matrix effect and current ways for end-point measurement, focusing on so called hyphenated techniques as a combination of chromatographic separation and mass spectrometry. Finally, the informative value of their determination as markers of male fertility disorders (impaired spermatogenesis, abnormal sperm parameters, varicocele) is discussed, along with instances where measuring their levels in seminal plasma is preferable to measurement of levels in blood plasma.

Les spermatozoïdes ne représentent que 2 à 25% du liquide séminal, le reste étant constitué par le plasma séminal. Le plasma séminal est un cocktail de composés organiques et non organiques comprenant des hormones qui font office de source de substances nutritives pour le développement et la maturation des spermatozoïdes, qui les protègent de l'infection et leur permettent de surmonter l'environnement immunologique et chimique de l'appareil reproducteur féminin. La présente revue propose une vue d'ensemble des hormones retrouvées dans le plasma séminal de l'homme, l'accent étant particulièrement mis sur les hormones reproductives. La participation de ces dernières au processus de fécondation est discutée, y compris leur rôle indispensable dans la fécondation de l'ovocyte. L'origine de chacune des hormones retrouvées dans le plasma séminal est décrite, ainsi que les différences de leurs concentrations dans le plasma séminal et dans le plasma sanguin. Une partie de cette revue est dévolue aux méthodes de mesure, en soulignant des exemples particuliers où elles diffèrent des mesures dans le plasma sanguin. Ces méthodes comprennent les techniques de séparation, qui surmontent les effets matriciels et les procédures actuelles de critère de mesure, en se concentrant sur les techniques dites de couplage comme la combinaison de la séparation chromatographique et de la spectrométrie de masse. Enfin, la valeur informative de la détermination de ces hormones en tant que marqueurs des anomalies de la fertilité masculine (spermatogenèse altérée, paramètres spermatiques anormaux, varicocèle) est discutée, ainsi que les situations où la mesure de leurs taux dans le plasma séminal est préférable à celle du plasma sanguin.

Determination of selected bisphenols, parabens and estrogens in human plasma using LC-MS/MS.

In this study, a novel liquid chromatography - tandem mass spectrometry method for the simultaneous determination of bisphenols (BPA, BPS, BPF, BPAF), parabens (methyl-, ethyl-, propyl-, butyl-, benzyl-paraben) and estrogens (estrone, estradiol, estriol) in human plasma is presented. Since all analytes possess the phenolic group, dansyl chloride derivatization was applied in order to gain high sensitivity. The method was validated according to FDA guidelines, and all validation requirements were satisfactory. The lower limits of quantifications were 41.6, 54.9, 43.5 and 150.8pg/mL for BPA, BPS, BPF and BPAF; 172, 149, 171, 134 and 202pg/mL for methyl-, ethyl-, propyl-, butyl- and benzyl-paraben; 10.5, 6.7 and 9.4pg/mL for estrone, estradiol and estriol, respectively. This is the first method allowing the determination of plasma bisphenols, parabens and estrogens in one run, and also the first determination of BPF levels in human plasma. The method was used to examine the plasma levels of healthy normospermic men, where three times higher plasma levels of BPF than BPA were found.

Associations of bisphenol A and polychlorinated biphenyls with spermatogenesis and steroidogenesis in two biological fluids from men attending an infertility clinic.

BACKGROUND: In the testis, steroid hormones play an important role in spermatogenesis, the production of semen, and the maintenance of secondary sex characteristics and libido. They may also play a role as a target for substances called endocrine disruptors (EDs). As yet, however, no complex study has been conducted evaluating the relationships between EDs and the steroid spectrum in the plasma and seminal plasma. OBJECTIVES: To shed more light into mechanisms of EDs and the effects of bisphenol A (BPA) and polychlorinated biphenyls (PCBs) on human spermatogenesis and steroidogenesis. METHODS: We determined BPA and 11 steroids in the plasma and seminal plasma of 191 men with different degrees of fertility, using a newly developed liquid-chromatography mass spectrometry method. Concurrently, plasma levels of 6 congeners of PCBs, gonadotropins, selenium, zinc and homocysteine were measured. Partial correlations adjusted for age, BMI and abstinence time were performed to evaluate relationships between these analytes. RESULTS: Seminal BPA, but not plasma BPA, was negatively associated with sperm concentration (r=-0.198; p=0.009), sperm count (r=-0.178; p=0.018) and morphology (r=-0.160; p=0.044). Divergent and sometimes opposing associations of steroids and BPA were found in both body fluids. The sum of PCB congeners was negatively associated with testosterone, free testosterone, the free androgen index and dihydrotestosterone in plasma. CONCLUSION: BPA may negatively contribute to the final state of sperm quality. Moreover, our data indicate that BPA influences human gonadal and adrenal steroidogenesis at various steps. Environmental levels of PCBs negatively correlated with androgen levels, but surprisingly without negative effects on sperm quality.

Endocrine disruptors and other inhibitors of 11ß-hydroxysteroid dehydrogenase 1 and 2: Tissue-specific consequences of enzyme inhibition.

Numerous chemicals in the environment have the ability to interact with the endocrine system. These compounds are called endocrine disruptors (EDs). Exposure to EDs represents one of the hypotheses for decreasing fertility, the increased risk of numerous cancers and obesity, metabolic syndrome and type 2 diabetes. There are various mechanisms of ED action, one of which is their interference in the action of 11ß-hydroxysteroid dehydrogenase (11ßHSD) that maintains a balance between active and inactive glucocorticoids on the intracellular level. This enzyme has two isoforms and is expressed in various tissues. Inhibition of 11ßHSD in various tissues can have different consequences. In the case of EDs, the results of exposure are mainly adverse; on the other hand pharmaceutically developed inhibitors of 11ßHSD type 1 are evaluated as an option for treating metabolic syndrome, as well as related diseases and depressive disorders. This review focuses on the effects of 11ßHSD inhibitors in the testis, colon, adipose tissue, kidney, brain and placenta.

Steroids and endocrine disruptors--History, recent state of art and open questions.

This introductory chapter provides an overview of the levels and sites at which endocrine disruptors (EDs) affect steroid actions. In contrast to the special issue of Journal of Steroid Biochemistry and Molecular Biology published three years ago and devoted to EDs as such, this paper focuses on steroids. We tried to point to more recent findings and opened questions. EDs interfere with steroid biosynthesis and metabolism either as inhibitors of relevant enzymes, or at the level of their expression. Particular attention was paid to enzymes metabolizing steroid hormones to biologically active products in target cells, such as aromatase, 5α-reductase and 3ß-, 11ß- and 17ß-hydroxysteroid dehydrogenases. An important target for EDs is also steroid acute regulatory protein (StAR), responsible for steroid precursor trafficking to mitochondria. EDs influence receptor-mediated steroid actions at both genomic and non-genomic levels. The remarkable differences in response to various steroid-receptor ligands led to a more detailed investigation of events following steroid/disruptor binding to the receptors and to the mapping of the signaling cascades and nuclear factors involved. A virtual screening of a large array of EDs with steroid receptors, known as in silico methods (≡computer simulation), is another promising approach for studying quantitative structure activity relationships and docking. New data may be expected on the effect of EDs on steroid hormone binding to selective plasma transport proteins, namely transcortin and sex hormone-binding globulin. Little information is available so far on the effects of EDs on the major hypothalamo-pituitary-adrenal/gonadal axes, of which the kisspeptin/GPR54 system is of particular importance. Kisspeptins act as stimulators for hormone-induced gonadotropin secretion and their expression is regulated by sex steroids via a feed-back mechanism. Kisspeptin is now believed to be one of the key factors triggering puberty in mammals, and various EDs affect its expression and function. Finally, advances in analytics of EDs, especially those persisting in the environment, in various body fluids (plasma, urine, seminal fluid, and follicular fluid) are mentioned. Surprisingly, relatively scarce information is available on the simultaneous determination of EDs and steroids in the same biological material. This article is part of a Special Issue entitled 'Endocrine disruptors & steroids'.

Development and validation of LC-MS/MS method for quantification of bisphenol A and estrogens in human plasma and seminal fluid.

Bisphenol A (BPA) is a widely known endocrine disruptor with estrogenic, antiestrogenic or antiandrogenic properties. BPA could interfere with estrogen metabolism as well with receptor-mediated estrogen actions. Both environmental BPA and estrogens may be traced in body fluids, of which, besides the blood plasma, the seminal fluid is of particular interest regarding their possible interactions in the testis. The method for simultaneously determining BPA and estrogens is then needed, taking into account that their concentrations in these body fluid may differ. Here the method was developed and validated for measurements of BPA, estrone (E1), estradiol (E2) and estriol (E3) in blood plasma and seminal plasma using liquid chromatography-tandem mass spectrometry. Due to the phenolic moiety of all compounds, dansyl chloride derivatization could be used. The analytical criteria of the method with respect to expected concentration of the analytes were satisfactory. The lower limits of quantifications (LLOQ) amounted to 43.5, 4.0, 12.7, 6.7 pg/mL for plasma BPA, E1, E2 and E3, and 28.9, 4.9, 4.5, 3.4 pg/mL for seminal BPA, E1, E2 and E3, respectively. The concentrations of individual steroids differed between body fluids. To the best of our knowledge, this is the first method that enabled the measurement of estrogens and BPA together in one run. The concentrations of E1, E2 and for the first time also of E3 in seminal plasma in normospermic men are reported.

Steroid hormones in prediction of normal pressure hydrocephalus.

Normal pressure hydrocephalus (NPH) is a treatable neurological disorder affecting elderly people with the prevalence increasing with age. NPH is caused by abnormal cerebrospinal fluid (CSF) reabsorption and manifested as a balance impairment, urinary incontinence and dementia development. These symptoms are potentially reversible if recognized early. Diagnosis of NPH is difficult and can be easily mistaken for other neurodegenerative disorders, which makes NPH one of the major misdiagnosed diseases worldwide. The aim of the study was to find out the appropriate combination of indicators, based on CSF steroids, which would contribute to a clearer NPH diagnosis. The levels of CSF cortisol, cortisone, dehydroepiandrosterone (DHEA), 7α-OH-DHEA, 7ß-OH-DHEA, 7-oxo-DHEA, 16α-OH-DHEA and aldosterone (all LC-MS/MS) were determined in our patients (n=30; NPH, 65-80 years) and controls (n=10; 65-80 years). The model of orthogonal projections to latent structures (OPLS) was constructed to predict NPH. Cortisone, 7α-OH-DHEA, 7ß-OH-DHEA, 7-oxo-DHEA, aldosterone, 7α-OH-DHEA /DHEA, 7-oxo-DHEA/7α-OH-DHEA, 7ß-OH-DHEA/7-oxo-DHEA and 16α-OH-DHEA/DHEA in the CSF were identified as the key predictors and the model discriminated patients from controls with 100% sensitivity and 100% specificity. The suggested model would contribute to early and accurate NPH diagnosis, enabling promptly treatment of the disease.

Hormones and the blood-brain barrier.

Hormones exert many actions in the brain, and brain cells are also hormonally active. To reach their targets in brain structures, hormones must overcome the blood-brain barrier (BBB). The BBB is a unique device selecting desired/undesired molecules to reach or leave the brain, and it is composed of endothelial cells forming the brain vasculature. These cells differ from other endothelial cells in their almost impermeable tight junctions and in possessing several membrane structures such as receptors, transporters, and metabolically active molecules, ensuring their selection function. The main ways how compounds pass through the BBB are briefly outlined in this review. The main part concerns the transport of major classes of hormones: steroids, including neurosteroids, thyroid hormones, insulin, and other peptide hormones regulating energy homeostasis, growth hormone, and also various cytokines. Peptide transporters mediating the saturable transport of individual classes of hormones are reviewed. The last paragraph provides examples of how hormones affect the permeability and function of the BBB either at the level of tight junctions or by various transporters.

Determination of seven selected neuro- and immunomodulatory steroids in human cerebrospinal fluid and plasma using LC-MS/MS.

Dehydroepiandrosterone (DHEA) and its 7-oxo- and 7-hydroxy-metabolites occurring in the brain are considered neurosteroids. Metabolism of the latter is catalysed by 11ß-hydroxysteroid dehydrogenase (11ß-HSD) which also interconverts cortisol and cortisone. The concurrent metabolic reaction to DHEA 7-hydroxylation is the formation of 16α-hydroxy-DHEA. The LC-MS/MS method using triple stage quadrupole-mass spectrometer was developed for simultaneous quantification of free DHEA, 7α-hydroxy-DHEA, 7ß-hydroxy-DHEA, 7-oxo-DHEA, 16α-hydroxy-DHEA, cortisol and cortisone in human plasma and cerebrospinal fluid (CSF). The method employs 500 µL of human plasma and 3000 µL of CSF extracted with diethyl ether and derivatized with 2-hydrazinopyridine. It has been validated in terms of sensitivity, precision and recovery. In plasma, the following values were obtained: limit of detection: 2-50p g/mL; limit of quantification: 5-140 pg/mL; within-day precision 0.58-14.58%; between-day precision: 1.24-13.89% and recovery: 85-113.2%). For CSF, the values of limit of detection: 2-28 pg/mL; limit of quantification: 6-94 pg/mL; within-day precision; 0.63-5.48%; between-day precision: 0.88-14.59% and recovery: 85.1-109.4% were acquired. Medians and concentration ranges of detected steroids in plasma and CSF are given in subjects with excluded normal pressure hydrocephalus (n=37; 65-80 years). The method enables simultaneous quantification of steroids important for the estimation of 11ß-HSD activity in human plasma and CSF. It will be helpful in better understanding various degenerative diseases development and progression.

Glucose homeostasis and insulin resistance: prevalence, gender differences and predictors in adolescents.

BACKGROUND: Adolescence, due to transient pubertal insulin resistance (IR), is associated with a higher risk for disturbances of glucose metabolism. The aim of our study was 1) to investigate the prevalence of disturbances of glucose metabolism, 2) to define gender specific homeostasis model assessment of insulin resistance (HOMA-IR) thresholds associated with increased cardiometabolic risks and 3) to provide predictors of HOMA-IR. METHODS: The studied cohort consisted of Czech adolescents aged 13.0-17.9 years: 1,518 individuals of general population and three studied groups according weight category (615 normal weight, 230 overweight and 683 obese). The prevalence of IR, impaired fasting glucose (IFG) and type 2 diabetes was assessed. Risky HOMA-IR thresholds based on components of metabolic syndrome were investigated. HOMA-IR prediction was calculated taking into account age, blood pressure, multiple anthropometric, biochemical and hormonal parameters. RESULTS: In general population cohort, the prevalence of IFG and type 2 diabetes was 7.0% and <0.5%, respectively. Boys regardless of weight presented significantly higher levels of blood glucose and higher prevalence of IFG than girls. Obese boys were found more insulin resistant than obese girls. HOMA-IR thresholds of 3.6 for girls and 4.4 for boys were associated with increased cardiometabolic risks. For both genders, the model of HOMA-IR prediction was composed of age, BMI, ratio of free triiodthyronine to free thyroxine, gamma-glutamyltransferase activity and levels of triglycerides and sex hormone-binding globulin. CONCLUSIONS: The type 2 diabetes in adolescents, including those who were obese, was rarely diagnosed. Obese adolescent boys were at greater risk for IR and for IFG than obese girls. In adolescence, thresholds of HOMA-IR in contrast to predictors were found gender specific.

Difference of neuro- and immunomodulatory steroids and selected hormone and lipid concentrations between Toxoplasma-free and Toxoplasma-infected but not CMV-free and CMV-infected schizophrenia patients.

OBJECTIVES: Toxoplasma gondii, the protozoan parasite infecting about 30% population worldwide, is suspected to be the etiological agent of certain form of schizophrenia disease. Toxoplasma is known to change levels of certain neurotransmitters, cytokines and several hormones in both infected animals and humans. A common feature of toxoplasmosis and schizophrenia is a disorder of immune system. METHODS: Here we studied the levels of five neuro- and immunomodulatory steroids, selected hormones and lipids in sera of 173 schizophrenia patients. RESULTS: Toxoplasma infected schizophrenia patients expressed only insignificantly lower concentration of neuro- and immunomodulatory DHEA metabolites. Infected women had higher concentration of glucose while infected men had higher concentration of cholesterol and LDL cholesterol. No significant effect of human cytomegalovirus infection on the concentration of the above parameters was observed. The difference in the concentration of DHEA metabolites faded with the decrease of the concentration of anti-Toxoplasma IgG antibodies (i.e. with the duration of Toxoplasma infection) while the difference in the concentration of cholesterol and LDL-cholesterol increased with the decrease of the concentration of anti-Toxoplasma IgG antibodies. The prevalence of toxoplasmosis in male (53.2%) but not female (29.8%) schizophrenia patients was unusually high in comparison with prevalence of toxoplasmosis in a general population. CONCLUSION: Our results provided an explanation for seemingly decreasing prevalence of toxoplasmosis in schizophrenia patients observed in current studies (increased concerns about the rights of patients resulting in absence of non-cooperative Toxoplasma-positive patients in the study population) and suggest possible explanation for reported positive correlation between prevalence of toxoplasmosis and incidence of cardiovascular diseases (accelerated atherosclerotic development due to increased level of cholesterol and LDL in Toxoplasma infected humans).

Selected pro- and anti-inflammatory cytokines in cerebrospinal fluid in normal pressure hydrocephalus.

OBJECTIVES: Normal pressure hydrocephalus (NPH) is a treatable neurological syndrome developing in the elderly. It is characterized by balance impairment, urinary incontinence and dementia development caused by disorders in the cerebrospinal fluid (CSF) circulation. The diagnosis can be easily mistaken for other neurodegenerative diseases, which are often accompanied by inflammation and the production of cytokines. The aim of our study was to determine and compare selected CSF and plasma cytokines with respect to their informative value for laboratory diagnostics of NPH. METHODS: The levels of IL-1ß, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, INF-γ, sCD40L and TNF-α were measured in the CSF and plasma in age-matched subjects with NPH (n=20) and controls (n=20) by multiplex assay. RESULTS: CSF IL-1ß, IL-6 and IL-10 were significantly increased on the 1st day of lumbar drainage in NPH (p<0.01). No significant changes were observed in the plasma. The CSF cytokines were one to three orders of magnitude higher compared to the plasma. CONCLUSION: CSF can better show the neurodegenerative changes in the brain. The cytokines IL-1ß, IL-6 and IL-10 may be helpful in NPH diagnostics.

Steroids in semen, their role in spermatogenesis, and the possible impact of endocrine disruptors.

The data on hormonal steroids in the human seminal plasma and their role in spermatogenesis are summarized. The seminal steroid levels need not correlate with the blood plasma levels. The recent reports showed that androgen, especially dihydrotestosterone, and the estrogen levels in the seminal fluid may be used as the markers of spermatogenesis impairment. The estradiol concentration in the seminal plasma was higher than in the blood plasma, and its levels were significantly increased in men with impaired spermatogenesis. A good indicator for predicting the normal spermatogenesis, therefore, seems to be the testosterone/estradiol ratio. The seminal plasma also contains significant amounts of cortisol, which influences the androgen biosynthesis through its receptors in the Leydig cells. The local balance between cortisol and inactive cortisone is regulated by 11ß-hydroxysteroid dehydrogenase, the activity of which may be affected by the environmental chemicals acting as the endocrine disruptors (EDCs). These compounds are believed to participate in worsening the semen quality - the sperm count, motility, and morphology, as witnessed in the recent last decades. As to the steroids' role in the testis, the EDCs may act as antiandrogens by inhibiting the enzymes of testosterone biosynthesis, as the agonists or antagonists through their interaction with the steroid hormone receptors, or at the hypothalamic-pituitary-gonadal axis. Surprisingly, though the EDCs affect the steroid action in the testis, there is no report of a direct association between the concentrations of steroids and the EDCs in the seminal fluid. Therefore, measuring the steroids in the semen, along with the various EDCs, could help us better understand the role of the EDCs in the male reproduction.

Determination of steroid metabolome as a possible tool for laboratory diagnosis of schizophrenia.

Metabolomic studies represent a promising tool for early diagnosis of schizophrenia. The aim of this study was to find differences in the steroid spectrum in patients and controls, and to assess the diagnosis of schizophrenia by building a predictive model based on steroid data. Thirty-nine serum steroids (22 neuroactive steroids and their metabolites and 17 polar conjugates) representing steroid metabolome were measured by gas chromatography-mass spectrometry in 22 drug-naive (first episode) schizophrenia patients (13 men and 9 women) before and after six-month treatment with atypical antipsychotics. The results were compared to the data from healthy subjects (22 males, 25 females). In summary the following significant differences were found: (1) In both sexes higher levels of pregnenolone sulfate and sulfated 5α- as well as 5ß-saturated metabolites of C21-steroids in progesterone metabolic pathway were found in patients, pointing to decreased activity of sulfatase. (2) In a few instances decreased levels of the respective 5α-metabolites of C21 steroids were found in patients. (3) As C19 steroids concern, in both sexes there were considerably lowered levels of 5ß-reduced metabolites in patients. On the other hand, with only a few exceptions, the treatment did not significantly influence most steroid levels. Further, to assess the relationships between schizophrenia status and steroid levels and to build the predictive model of schizophrenia, multivariate regression with reduction of dimensionality (the method of orthogonal projections to latent structures, OPLS) was applied. Irrespective of the small number of patients, use of this model enabled us to state the diagnosis of schizophrenia with almost 100% sensitivity. Our findings suggest that the assessment of steroid levels may become a valid and accurate laboratory test in psychiatry. A limitation of our study is the absence of subjects with a diagnosis other than schizophrenia, so we cannot conclude whether the results are specific for schizophrenia. On the other hand, steroid metabolome model may be used as a diagnostic tool for further studies.

The relation of cortisol and sex hormone levels to results of psychological, performance, IQ and memory tests in military men and women.

BACKGROUND: Cortisol, along with other hormones of hypothalamo-pituitary-adrenal axis, belongs to one of the main factors influencing psychological and pathognomic factors, intelligence, and memory. METHODS: The aim of our study was to review a large battery of psychological, performance, IQ and memory tests as to their relation with cortisol, testosterone and estrogen levels in groups of 100 men and 93 women who attended the Central Military Hospital in Prague for regular entrance psychological examinations for military personnel. RESULTS: In men, we detected positive correlations between cortisol and emotional lability, and negative correlations with impulsivity, while in women hypochondria and psychopathology were negatively correlated, and aggression measured with the Meili selective memory test had a positive relation to cortisol level. Testosterone correlated positively with emotional liability and negatively with impulsivity in men, and negatively with hypochondria and psychasteny, indirect aggression, irritability and paranoia in women. Estradiol correlated positively with psychopathology in men, and negatively with phobia. It was positively correlated with negativism in women. No clear correlation was observed between the concentration of steroid hormones and psychomotor performance or intelligence. CONCLUSIONS: Concentrations of steroid hormones correlate with results of several psychological tests, the sign and magnitude of these correlations, however, very often differ in military men and women.