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 3β-, 11β- and 17β-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'.

• MeSH
• 17-Hydroxysteroid Dehydrogenases genetics   metabolism   MeSH
• 3-Oxo-5-alpha-Steroid 4-Dehydrogenase genetics   metabolism   MeSH
• History, 20th Century MeSH
• History, 21st Century MeSH
• Endocrine Disruptors history   pharmacology   MeSH
• Sex Hormone-Binding Globulin genetics   metabolism   MeSH
• Humans MeSH
• Gonadal Steroid Hormones history   metabolism   MeSH
• Gene Expression Regulation MeSH
• High-Throughput Screening Assays MeSH
• Signal Transduction MeSH
• Molecular Docking Simulation MeSH
• Receptors, Steroid genetics   metabolism   MeSH
• Pituitary-Adrenal System drug effects   metabolism   MeSH
• Hypothalamo-Hypophyseal System drug effects   metabolism   MeSH
• Transcortin genetics   metabolism   MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• History, 20th Century MeSH
• History, 21st Century MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Historical Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Předmětem řešení projektu je podrobná analýza a porovnání testů osy hypotalamus-hypofýza-nadledviny a analýza metabolitů kortizolu v průběhu těchto testů. Na základě širokého zastoupení steroidů simultánně měřených v jednotlivých vzorcích v průběhu testů zhodnotíme klíčové prvky podílející se na patofyziologii adrenální insuficience.Tento přístup nám umožní vytvoření novějších diagnostických algoritmů hypokortikalismu a norem pro kortizol ve slinách. Získáme racionální podklady pro časnou diagnostiku nemocných s postižením osy hypotalamus- hypofýza – nadledviny a také možnost včasně odhalit poruchu nadledvin u žen užívajících estrogenní terapii nebo u pacientů se změněnými koncentracemi vazebných proteinů pro kortizol, u kterých je stále hodnocení poruchy osy hypotalamus- hypofýza – nadledviny problematické. Objasnění této problematiky umožní navržení nových diagnostických a terapeutických postupů těchto onemocnění, a tím zkvalitnění péče o pacienty.; A subject of solution of the project is a detailed analysis and a comparison of hypothalamic-pituitary-adrenal axis tests and cortisol metabolites analysis during these tests. Based on a wide range of steroids simulateously measured in each sample, we will evaluate key elements contributing to the pathophysiology of adrenal insufficiency. This procedure will enable to design new diagnostic algorithms of hypocorticalism and standards for salivary cortisol. Rational supporting data for early diagnostic of patients with hypothalamic-pituitary-adrenal axis disorder will be acquired as well as a possibility to reveal adrenal disorder in patients on estrogen therapy or with altered levels of cortisol-binding proteins whose hypothalamic-pituitary-adrenal axis evaluation is always problematic. Clarifying these issues will propose new diagnostic and therapeutic procedures of such disorders resulting in enhancing quality of patient care.

• MeSH
• Addison Disease diagnosis   MeSH
• Adrenal Insufficiency MeSH
• Adrenocorticotropic Hormone analysis   MeSH
• Early Diagnosis MeSH
• Estrogen Replacement Therapy MeSH
• Hydrocortisone MeSH
• Hypoglycemia MeSH
• Neurotransmitter Agents MeSH
• Pituitary-Adrenal System MeSH
• Hypothalamo-Hypophyseal System MeSH
• Transcortin MeSH

• Conspectus
• Fyziologie člověka a srovnávací fyziologie
• NML Fields
• endokrinologie
• NML Publication type
• závěrečné zprávy o řešení grantu IGA MZ ČR

Předmětem řešení projektu je bližší charakteristika funkčního stavu nadledvin a ovarií u autoimunitního diabetes mellites typu 1 mladých dospělých. Formou průřezové studie budou získána data o výskytu subklinických poruch nadledvin pomocí 1ug stimulačního ACTH testu. Změny v diurnálním rytmu kortisolu budou sledovány pomocí volného kortisolu ve slinách a v moči. Ve vztahu k funkčním poruchám budeme sledovat i autoimunitní projevy proti nadledvině a metabolismus kortisolu (kortison acetátový test). Dálebude sledován výskyt a příčiny poruch menstruačního cyklu u žen v této skupině, jejich vztah ke stavu nadledvin resp. osy HPA. Proto budou sledovány hyperandrogenní projevy laboratorně i klinicky, přítomnost PCO a autoimunitní projevy proti ovariím.; The subject of the proposed project is the more datailed characterisation of functional status of adrenal glands and ovaries in in young adult patients with autoimmune type 1 diabetes mellitus. By means of cross-sectional study we gain data concerning presence of subclinical forms of adrenal glands using 1ug ACTH stimulation test. The changes of circadian rhythm of cortisol will be studied by determination of free salivary cortisol and cortisol urinary excretion. Autoimmunity against adrenal gland in relation to its functional disorder and metabolism of cortisol (cortisone acetate test) will be focused too. The presence and causes of menstrual cycle disorders and their relation to functional status of adrenal gland and hypothalamus-pituitary-adrenal axis will be examined in women. For this purpose laboratory and clinical signs of hyperandrogenaemia, presence of PCO and autoimmne affection of ovaries will be investigated.

• MeSH
• 11-beta-Hydroxysteroid Dehydrogenases MeSH
• Adrenogenital Syndrome immunology   MeSH
• Adrenal Cortex Function Tests MeSH
• Adrenocorticotropic Hormone deficiency   secretion   MeSH
• Polyendocrinopathies, Autoimmune MeSH
• Diabetes Mellitus, Type 1 physiopathology   MeSH
• Diagnostic Techniques, Endocrine MeSH
• Hydrocortisone analysis   secretion   MeSH
• Hyperandrogenism MeSH
• Adrenal Cortex immunology   MeSH
• Young Adult MeSH
• Pituitary-Adrenal System MeSH
• Hypothalamo-Hypophyseal System MeSH
• Transcortin MeSH
• Check Tag
• Young Adult MeSH
• Male MeSH
• Female MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• endokrinologie
• diabetologie
• NML Publication type
• závěrečné zprávy o řešení grantu IGA MZ ČR

V játrech tvořené plazmatické transportní proteiny selektivně vážící steroidy – sexuální hormony vážící globulin (SHBG) a kortikosteroidy vážící globulin (CBG, transkortin) vedle toho, že regulují aktuální hladiny příslušných hormonů a jejich vstup do cílových tkání, mají i vlastní hormonální aktivitu. SHBG tím, že je zapojen do tří endokrinních os – gonadální, tyroidální a inzulární, je vhodným ukazatelem v laboratorní diagnostice nejen poruch gonadální funkce, ale i poruch spojených s inzulinorezistencí, jakou je diabetes mellitus, obezita či syndrom polycystických ovárií (PCOS). Jeho využití bylo uvažováno i pro diagnostiku subklinických poruch funkce štítné žlázy. Transkortin zatím nepatří mezi běžné analyty v endokrinologii a klinické biochemii, avšak lze očekávat jeho širší uplatnění v diagnostice poruch glykoregulace. Zajímavé jsou jeho snížené hladiny u chronického únavového syndromu.

Hepatic plasma transport proteins selectively binding steroids - sex hormone-binding globulin (SHBG) and corticosteroidbinding globulin (CBG, transcortin), besides their regulatory role in control of actual hormone concentration and their transprt to target tissues, possess their inherent hormonal activity. SHBG, by virtue of its involvement in three endocrine axes – gonadal, insular and thyroidal, represents a suitable parameter for laboratory diagnostics not only of gonadal disorders, but also of those associated with insulinoresistance as diabetes mellitus, obesity or polycystic ovary syndrome (PCOS). In addition its use was considered as a possible tool for laboratory diagnostics of subclinical thyroid function disorders.. Transcortin so far does not belong to current analytes in endocrinology, and clinical biochemistry, but its broader use in diagnostics of impairment of glycoregulation may be expected. Of interest are its low levels in patients with chronic fatigue syndrome.

• Keywords
• sexuální hormony vážící globulin, kortikosteroidy vážící globulin, endokrinní regulace, laboratorní diagnostika,
• MeSH
• Diagnostic Techniques, Endocrine MeSH
• Sex Hormone-Binding Globulin diagnostic use   MeSH
• Insulin Resistance MeSH
• Glucose Intolerance diagnosis   blood   MeSH
• Transcortin diagnostic use   MeSH
• Carrier Proteins metabolism   MeSH

• MeSH
• Dehydroepiandrosterone diagnostic use   blood   MeSH
• Dehydroepiandrosterone Sulfate diagnostic use   blood   MeSH
• Hydrocortisone diagnostic use   blood   MeSH
• Humans MeSH
• Shock, Septic MeSH
• Pituitary-Adrenal System physiopathology   MeSH
• Hypothalamo-Hypophyseal System physiopathology   MeSH
• Transcortin diagnostic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Overall MeSH

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, lowdose 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.

• MeSH
• Adrenal Cortex Function Tests methods   utilization   MeSH
• Adrenocorticotropic Hormone diagnostic use   blood   MeSH
• Financing, Organized utilization   MeSH
• Hydrocortisone administration & dosage   diagnostic use   blood   MeSH
• Menstrual Cycle MeSH
• Salivary Glands enzymology   drug effects   MeSH
• Saliva enzymology   drug effects   MeSH
• Transcortin diagnostic use   isolation & purification   MeSH
• Women MeSH

• MeSH
• Biological Transport MeSH
• Hydrocortisone metabolism   MeSH
• Liver cytology   metabolism   MeSH
• Rats MeSH
• Cell Membrane Permeability MeSH
• Transcortin metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH

• MeSH
• Adrenal Cortex Hormones metabolism   MeSH
• Blood Proteins metabolism   MeSH
• Transcortin metabolism   MeSH
• Protein Binding MeSH