Through their receptors at each level of hypothalamo-pituitary-gonadal axis glucocorticoid excess, either endogenous or administered or stress-induced, could affect steroid production in the testis and thus male fertility. The main ways by which glucocorticoids act are as follows: 1) Affecting gonadoliberin and LH synthesis and release through glucocorticoid receptors in hypothalamic neurons and pituitary gonadotropes. 2) By so far not clearly evidenced reduction of the number of LH receptors on the membrane of Leydig cells. 3) By affecting expression and function of steroidogenic enzymes in the testis. 4) By regulation of in situ access of glucocorticoid to its target cells in the testis. 5) By promotion Leydig cell apoptosis. The review provides a survey of physiological and molecular mechanisms staying behind these effects. It does not deal with the clinical effects of glucocorticoid treatment which would substantially exceed the scope of the pater.

• MeSH
• glukokortikoidy farmakologie   MeSH
• lidé MeSH
• steroidy biosyntéza   MeSH
• testis účinky léků   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• glukokortikoidy MeSH
• steroidy MeSH

The regulation of drug-metabolizing cytochrome P450 enzymes (CYP) is a complex process involving multiple mechanisms. Among them, transcriptional regulation through ligand-activated nuclear receptors is the crucial mechanism involved in hormone-controlled and xenobiotic-induced expression of drug-metabolizing CYPs. In this article, we focus, in detail, on the role of the glucocorticoid receptor (GR) in the transcriptional regulation of human drug-metabolizing CYP enzymes and the mechanisms of the regulation. There are at least three distinct transcriptional mechanisms by which GR controls the expression of CYPs: 1) direct binding of GR to a specific gene-promoter sequence called the glucocorticoid responsive element (GRE); 2) indirect binding of GR in the form of a multiprotein complex to gene promoters without a direct contact between GR and promoter DNA; and 3) up- or downregulation of other CYP transcriptional regulators or nuclear receptors (i.e., transcriptional regulatory cross-talk). However, due to the general effect of glucocorticoids on numerous cellular pathways and functions, the net transcriptional effect of glucocorticoids on drug-metabolizing enzymes is usually a combination of several mechanisms. Since synthetic glucocorticoids are widely prescribed in human pharmacotherapy for the treatment of many diseases, comprehensive understanding of the transcriptional regulation of drug-metabolizing CYPs via GR with respect to glucocorticoid therapy or glucocorticoid hormonal status will aid in the development of efficient individualized pharmacotherapy without drug-drug interactions.

• MeSH
• glukokortikoidy chemie   metabolismus   MeSH
• léčivé přípravky metabolismus   MeSH
• lidé MeSH
• receptory glukokortikoidů fyziologie   MeSH
• systém (enzymů) cytochromů P-450 metabolismus   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• glukokortikoidy MeSH
• léčivé přípravky MeSH
• receptory glukokortikoidů MeSH
• systém (enzymů) cytochromů P-450 MeSH

Glucocorticoids (GCs) are effective for the treatment of many chronic conditions, but their use is associated with frequent and wide-ranging adverse effects including osteoporosis and growth retardation. The mechanisms that underlie the undesirable effects of GCs on skeletal development are unclear, and there is no proven effective treatment to combat them. An in vivo model that investigates the development and progression of GC-induced changes in bone is, therefore, important and a well-characterized pre-clinical model is vital for the evaluation of new interventions. Currently, there is no established animal model to investigate GC effects on skeletal development and there are pros and cons to consider with the different protocols used to induce osteoporosis and growth retardation. This review will summarize the literature and highlight the models and techniques employed in experimental studies to date.

• Klíčová slova
• glucocorticoids, growth, mouse, murine, osteoporosis, skeletal development,
• MeSH
• geneticky modifikovaná zvířata MeSH
• glukokortikoidy škodlivé účinky   MeSH
• kostra růst a vývoj   MeSH
• lidé MeSH
• modely nemocí na zvířatech * MeSH
• osteocyty účinky léků   MeSH
• osteoklasty účinky léků   MeSH
• osteoporóza chemicky indukované   MeSH
• poruchy růstu chemicky indukované   MeSH
• vývoj kostí účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• glukokortikoidy MeSH

The current Coronavirus disease outbreak requires that physicians work in collaboration with other physicians especially in intensive care and emergency units. To fight against this new disease, whose pathogenesis, effects, and results have not been clearly demonstrated, especially in patients with the pre-existing chronic disease, requires special expertise and perspectives. Due to the need for dynamic glucocorticoid treatment at different stages of the disease in patients with adrenal insufficiency, the existence of reports indicating that "coronavirus disease 2019" also affects the adrenal reserve, and the use of glucocorticoids also in advanced stages in patients with Coronavirus disease require this issue to be emphasized with precision. Herein, treatment of the pre-existing adrenal insufficiency in patients with actual Coronavirus disease and the effects of the this critical disease on the adrenal gland have been reviewed.

• Klíčová slova
• SARS-CoV-2, adrenal cortex, adrenal insufficiency, glucocorticoids, severe acute respiratory syndrome,
• MeSH
• adrenální insuficience komplikace   farmakoterapie   metabolismus   MeSH
• COVID-19 komplikace   terapie   MeSH
• fyziologický stres MeSH
• glukokortikoidy terapeutické užití   MeSH
• hormonální substituční terapie metody   MeSH
• hospitalizace MeSH
• hydrokortison terapeutické užití   MeSH
• lidé MeSH
• management nemoci MeSH
• nadledviny metabolismus   MeSH
• progrese nemoci MeSH
• SARS-CoV-2 MeSH
• zánět MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• glukokortikoidy MeSH
• hydrokortison MeSH

• Klíčová slova
• ADRENAL CORTEX HORMONES/therapy *, ILEITIS/prevention and control *,
• MeSH
• adheziva * MeSH
• glukokortikoidy * MeSH
• hormony kůry nadledvin terapie   MeSH
• ileitida prevence a kontrola   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adheziva * MeSH
• glukokortikoidy * MeSH
• hormony kůry nadledvin MeSH

The epithelial cells of choroid plexus (CP) in brain ventricles produce cerebrospinal fluid and act as the blood-cerebrospinal fluid barrier. In this study, we confirmed that CP in the 4th ventricle is composed of cellular oscillators that all harbor glucocorticoid receptors and are mutually synchronized to produce a robust clock gene expression rhythm detectable at the tissue level in vivo and in vitro. Animals lacking glucocorticoids (GCs) due to surgical removal of adrenal glands had Per1, Per2, Nr1d1 and Bmal1 clock gene rhythmicity in their CP significantly dampened, whereas subjecting them to daily bouts of synthetic GC analog, dexamethasone (DEX), reinforced those rhythms. We verified these in vivo effects using an in vitro model of organotypic CP explants; depending on the time of its application, DEX significantly increased the amplitude and efficiently reset the phase of the CP clock. The results are the first description of a PRC for a non-neuronal clock in the brain, demonstrating that CP clock shares some properties with the non-neuronal clocks elsewhere in the body. Finally, we found that DEX exhibited multiple synergic effects on the CP clock, including acute activation of Per1 expression and change of PER2 protein turnover rate. The DEX-induced shifts of the CP clock were partially mediated via PKA-ERK1/2 pathway. The results provide the first evidence that the GC rhythm strengthens and entrains the clock in the CP helping thus fine-tune the brain environment according to time of day.

• Klíčová slova
• choroid plexus, circadian clock, circadian entrainment, dexamethasone, glucocorticoids, phase–response curve,
• MeSH
• cirkadiánní hodiny * MeSH
• cirkadiánní proteiny Period genetika   metabolismus   MeSH
• dexamethason MeSH
• glukokortikoidy metabolismus   MeSH
• krysa rodu Rattus MeSH
• MAP kinasový signální systém MeSH
• nadledviny metabolismus   MeSH
• nucleus suprachiasmaticus metabolismus   MeSH
• plexus chorioideus metabolismus   MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cirkadiánní proteiny Period MeSH
• dexamethason MeSH
• glukokortikoidy MeSH
• Per2 protein, rat MeSH Prohlížeč

11β-Hydroxysteroid dehydrogenase type 1 (11HSD1) is a microsomal NADPH-dependent oxidoreductase which elevates intracellular concentrations of active glucocorticoids. Data obtained from mouse strains with genetically manipulated 11HSD1 showed that local metabolism of glucocorticoids plays an important role in the development of metabolic syndrome. Tissue specific dysregulation of 11HSD1 was also found in other models of metabolic syndrome as well as in a number of clinical studies. Here, we studied local glucocorticoid action in the liver, subcutaneous adipose tissue (SAT) and skeletal muscles of male and female Prague hereditary hypertriglyceridemic rats (HHTg) and their normotriglyceridemic counterpart, the Wistar rats. 11HSD1 bioactivity was measured as a conversion of [(3)H]11-dehydrocorticosterone to [(3)H]corticosterone or vice versa. Additionally to express level of active 11HSD1 protein, enzyme activity was measured in tissue homogenates. mRNA abundance of 11HSD1, hexoso-6-phosphate dehydrogenase (H6PDH) and the glucocorticoid receptor (GR) was measured by real-time PCR. In comparison with normotriglyceridemic animals, female HHTg rats showed enhanced regeneration of glucocorticoids in the liver and the absence of any changes in SAT and skeletal muscle. In contrast to females, the glucocorticoid regeneration in males of HHTg rats was unchanged in liver, but stimulated in SAT and downregulated in muscle. Furthermore, SAT and skeletal muscle exhibited not only 11-reductase but also 11-oxidase catalyzed by 11HSD1. In females of both strains, 11-oxidase activity largely exceeded 11-reductase activity. No dramatic changes were found in the mRNA expression of H6PDH and GR. Our data provide evidence that the relationship between hypertriglyceridemia and glucocorticoid action is complex and gender specific.

• MeSH
• 11-beta-hydroxysteroiddehydrogenasa typ 1 metabolismus   MeSH
• glukokortikoidy metabolismus   MeSH
• hypertriglyceridemie enzymologie   metabolismus   MeSH
• játra enzymologie   metabolismus   MeSH
• karbohydrátdehydrogenasy metabolismus   MeSH
• kortikosteron analogy a deriváty   metabolismus   MeSH
• kosterní svaly enzymologie   metabolismus   MeSH
• krysa rodu Rattus MeSH
• metabolický syndrom enzymologie   MeSH
• modely nemocí na zvířatech MeSH
• podkožní tuk enzymologie   metabolismus   MeSH
• potkani Wistar MeSH
• receptory glukokortikoidů genetika   metabolismus   MeSH
• sexuální faktory MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 11-beta-hydroxysteroiddehydrogenasa typ 1 MeSH
• 11-dehydrocorticosterone MeSH Prohlížeč
• galactose-6-phosphate dehydrogenase MeSH Prohlížeč
• glukokortikoidy MeSH
• karbohydrátdehydrogenasy MeSH
• kortikosteron MeSH
• receptory glukokortikoidů MeSH

• Klíčová slova
• ADRENAL CORTEX HORMONES/pharmacology *, CARTILAGE/transplantation *,
• MeSH
• chrupavka transplantace   MeSH
• glukokortikoidy * MeSH
• hormony kůry nadledvin farmakologie   MeSH
• lidé MeSH
• protézy a implantáty * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glukokortikoidy * MeSH
• hormony kůry nadledvin MeSH

The adult circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus is resilient to glucocorticoids (GCs). The fetal rodent SCN resembles that of the adult in its organization of GC-sensitive peripheral tissues. We tested the hypothesis that the fetal SCN clock is sensitive to changes in GC levels. Maternal GCs must pass through the placenta to reach the fetal SCN. We show that the maternal but not the fetal part of the placenta harbors the autonomous circadian clock, which is reset by dexamethasone (DEX) and rhythmically expresses Hsd11b2. The results suggest the presence of a mechanism for rhythmic GC passage through the placental barrier, which is adjusted according to actual GC levels. GC receptors are expressed rhythmically in the laser-dissected fetal SCN samples. We demonstrate that hypothalamic explants containing the SCN of the mPer2 Luc mouse prepared at embryonic day (E)15 spontaneously develop rhythmicity within several days of culture, with dynamics varying among fetuses from the same litter. Culturing these explants in media enriched with DEX accelerates the development. At E17, treatment of the explants with DEX induces phase advances and phase delays of the rhythms depending on the timing of treatments, and the shifts are completely blocked by the GC receptor antagonist, mifepristone. The DEX-induced phase-response curve differs from that induced by the vehicle. The fetal SCN is sensitive to GCs in vivo because DEX administration to pregnant rats acutely downregulates c-fos expression specifically in the laser-dissected fetal SCN. Our results provide evidence that the rodent fetal SCN clock may respond to changes in GC levels.

• Klíčová slova
• circadian clock, entrainment, glucocorticoids, mPer2 mouse, ontogenesis, suprachiasmatic nuclei,
• MeSH
• cirkadiánní hodiny účinky léků   genetika   fyziologie   MeSH
• cirkadiánní proteiny Period genetika   MeSH
• dexamethason farmakologie   MeSH
• glukokortikoidy farmakologie   fyziologie   MeSH
• hypothalamus fyziologie   MeSH
• krysa rodu Rattus MeSH
• myši MeSH
• nucleus suprachiasmaticus účinky léků   fyziologie   MeSH
• placenta fyziologie   MeSH
• plod fyziologie   MeSH
• těhotenství MeSH
• vývoj plodu * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cirkadiánní proteiny Period MeSH
• dexamethason MeSH
• glukokortikoidy MeSH
• Per2 protein, mouse MeSH Prohlížeč

Covid-19 pandemic affects heavily different health care systems. The most important factor/aspect is high number of hospitalized patients in countries with low level of infrastructure. Because of this, many therapeutic methods reducing the risk of more severe course of disease are now under development. The key part of this review is the STOIC trial, which is the largest, randomized trial assessing the effect of inhaled glucocorticoid treatment on the risk of hospitalization due to covid-19.

• Klíčová slova
• COVID-19, glucocorticoids,
• MeSH
• farmakoterapie COVID-19 * MeSH
• glukokortikoidy terapeutické užití   MeSH
• hospitalizace MeSH
• lidé MeSH
• pandemie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• glukokortikoidy MeSH