While there are hundreds of synthetic steroids conjugates with acids, sugars, proteins and other molecules, only two types of conjugates occur in living organisms, namely sulfates and glucuronides. Steroid glucuronidation in the human liver is the main mechanism controlling the levels and biological activity of unconjugated hormones, and glucuronides are their main excretion products. This process is generally irreversible. On the other hand, sulfates possess their own biological activity that differs from that of the unconjugated steroid, emphasizing the importance of steroid sulfatases and sulfotransferases. Due to their negative charge, steroid sulfates cannot cross the blood-cell barrier and have to use transporters. Their efflux is mediated by specific transporters of the ATP binding cassette protein group, which thus are further factors controlling their physiological effects. Steroid sulfates, especially dehydroepiandrosterone sulfate (DHEAS) are neuroactive steroids, with well-known effects as allosteric modulators of some neurotransmitter receptors, functioning as ion channels, such as gamma-aminobutyric acid, type A (GABAA) receptors or N-methyl-D-aspartate (NMDA) receptors. In this minireview, we highlight some recent findings of non-genomic steroid sulfate actions through specific G-protein coupled receptors (GPCR), which we believe show the way of further research. A few studies have even indicated that sulfates such as DHEAS may even indirectly regulate gene expression via ligand binding to the membrane receptor and, through G-protein and second messenger formation, activate proteins like cAMP Regulated Elements Binding protein (CREB), which then binds to regulated DNA elements of the expressed gene, in a "classical" genomic effect.
- MeSH
- biologický transport MeSH
- fosforylace MeSH
- lidé MeSH
- signální transdukce * MeSH
- sírany * metabolismus MeSH
- steroidy metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- O autorovi
- Stárka, Luboslav, 1930-2022 Autorita
Aged people are the most susceptible group to COVID-19 infection. Immunosenescence characterized by impairment of immune function with inflamm-aging contributes to pathophysiological alterations, among which endocrine and metabolic diseases are not exception. Diabetes, obesity along with impairment of disorders of thyroid functions are the most frequent ones, the common feature of which is failure of immune system including autoimmune processes. In the minireview we discussed how COVID-19 and aging impact innate and adaptive immunity, diabetes and selected neuroendocrine processes. Mentioned is also beneficial effect of vitamin D for attenuation of these diseases and related epigenetic issues. Particular attention is devoted to the role of ACE2 protein in the light of its intimate link with renin-angiotensin regulating system.
- MeSH
- adaptivní imunita MeSH
- COVID-19 imunologie metabolismus patofyziologie virologie MeSH
- endokrinní systém imunologie metabolismus patofyziologie virologie MeSH
- imunosenescence MeSH
- interakce hostitele a patogenu MeSH
- lidé MeSH
- přirozená imunita MeSH
- renin-angiotensin systém * MeSH
- SARS-CoV-2 imunologie patogenita MeSH
- stárnutí imunologie metabolismus MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
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 β 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.
- MeSH
- diabetes mellitus 2. typu krev etiologie patofyziologie prevence a kontrola MeSH
- inzulinová rezistence MeSH
- lidé MeSH
- nedostatek vitaminu D krev komplikace farmakoterapie patofyziologie MeSH
- vitamin D krev terapeutické užití MeSH
- vitaminy krev terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
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.
- MeSH
- androgeny metabolismus MeSH
- lidé MeSH
- nadledviny metabolismus MeSH
- pohlavní steroidní hormony metabolismus MeSH
- prostata metabolismus MeSH
- steroidy metabolismus MeSH
- testis metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- O autorovi
- Stárka, Luboslav, 1930- Autorita
Anthropogenic environmental pollutants affect many physiological, biochemical, and endocrine actions as reproduction, metabolism, immunity, behavior and as such can interfere with any aspect of hormone action. Microbiota and their genes, microbiome, a large body of microorganisms, first of all bacteria and co-existing in the host´s gut, are now believed to be autonomous endocrine organ, participating at overall endocrine, neuroendocrine and immunoendocrine regulations. While an extensive literature is available on the physiological and pathological aspects of both players, information about their mutual relationships is scarce. In the review we attempted to show various examples where both, endocrine disruptors and microbiota are meeting and can act cooperatively or in opposition and to show the mechanism, if known, staying behind these actions.
- MeSH
- endokrinní disruptory farmakologie MeSH
- fyziologie bakterií účinky léků MeSH
- gastrointestinální trakt účinky léků mikrobiologie MeSH
- látky znečišťující životní prostředí farmakologie MeSH
- lidé MeSH
- střevní mikroflóra účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
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
- MeSH
- analytická chemie dějiny normy MeSH
- chemické techniky analytické dějiny metody přístrojové vybavení MeSH
- chromatografie dějiny metody MeSH
- hmotnostní spektrometrie metody MeSH
- nemoci endokrinního systému krev moč MeSH
- radioimunoanalýza dějiny metody přístrojové vybavení MeSH
- steroidy * analýza krev moč MeSH
- Publikační typ
- práce podpořená grantem MeSH
