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
- endokrinní disruptory * MeSH
- lidé MeSH
- mozek MeSH
- neurodegenerativní nemoci * etiologie MeSH
- neurovývojové poruchy etiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
- MeSH
- duševní poruchy * etiologie MeSH
- lidé MeSH
- mikrobiota MeSH
- mozek MeSH
- střevní mikroflóra * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Resistance to steroid hormones presents a serious problem with respect to their mass use in therapy. It may be caused genetically by mutation of genes involved in hormonal signaling, not only steroid receptors, but also other players in the signaling cascade as co-regulators and other nuclear factors, mediating the hormone-born signal. Another possibility is acquired resistance which may develop under long-term steroid treatment, of which a particular case is down regulation of the receptors. In the review recent knowledge is summarized on the mechanism of main steroid hormone action, pointing to already proven or potential sites causing steroid resistance. We have attempted to address following questions: 1) What does stay behind differences among patients as to their response to the (anti)steroid treatment? 2) Why do various tissues/cells respond differently to the same steroid hormone though they contain the same receptors? 3) Are such differences genetically dependent? The main attention was devoted to glucocorticoids as the most frequently used steroid therapeutics. Further, androgen insensitivity is discussed with a particular attention to acquired resistance to androgen deprivation therapy of prostate cancer. Finally the potential causes are outlined of breast and related cancer(s) resistance to antiestrogen therapy.
- MeSH
- androgenní receptory metabolismus MeSH
- antagonisté hormonů metabolismus farmakologie terapeutické užití MeSH
- glukokortikoidy metabolismus farmakologie terapeutické užití MeSH
- léková rezistence účinky léků fyziologie MeSH
- lidé MeSH
- nádory prostaty farmakoterapie metabolismus MeSH
- nádory prsu farmakoterapie metabolismus MeSH
- pohlavní steroidní hormony metabolismus farmakologie terapeutické užití MeSH
- steroidní receptory metabolismus MeSH
- steroidy metabolismus farmakologie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
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-hydroxysteroidní dehydrogenasy genetika metabolismus MeSH
- 3-oxo-5-alfa-steroid-4-dehydrogenasa genetika metabolismus MeSH
- dějiny 20. století MeSH
- dějiny 21. století MeSH
- endokrinní disruptory dějiny farmakologie MeSH
- globulin vázající pohlavní hormony genetika metabolismus MeSH
- lidé MeSH
- pohlavní steroidní hormony dějiny metabolismus MeSH
- regulace genové exprese MeSH
- rychlé screeningové testy MeSH
- signální transdukce MeSH
- simulace molekulového dockingu MeSH
- steroidní receptory genetika metabolismus MeSH
- systém hypofýza - nadledviny účinky léků metabolismus MeSH
- systém hypotalamus-hypofýza účinky léků metabolismus MeSH
- transkortin genetika metabolismus MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- dějiny 20. století MeSH
- dějiny 21. století MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- historické články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Zdrojem steroidních hormonů vedle „klasických“ orgánů, jako jsou kůra nadledvin, gonády a placenta, jsou i některé další tkáně jako nervová tkáň včetně mozku, střeva, tuková tkáň a kůže. Metody molekulární biologie prokázaly v buňkách těchto tkání expresi klíčových enzymů steroidogeneze a steroidního metabolismu i proteinů zprostředkujících transport příslušných prekurzorů do mitochondrií. Lokálně tvořené hormony prostřednictvím svých receptorů zde spoluúčinkují s hormony z cirkulace s využitím para- a autokrinních mechanismů. Nadto některé z těchto tkání, především kůže, disponují vlastním paralelním řídícím systémem, imitujícím klasické zpětnovazebné hormonální osy. Uvádíme tyto skutečnosti s ohledem na terapeutický potenciál hormonálních steroidů a jejich syntetických analog.
The source of hormonal steroids are, besides “classical” organs as adrenocortex, gonads and placenta, also some other tissues as nervous system including brain, intestine, adipose cells and skin. Advances of molecular biology revealed there expression of the key steroidogenic enzymes, enzymes of steroid metabolism and also proteins mediating transport of the substrates into mitochondia. Locally formed steroids through their receptors act there parallely to circulating hormones using paracrine or autocrine mechanisms. In addition, some of these tissues, especially skin, possess autonomous, parallel regulating system, imitating classical feed-back hormonal axes. We are presenting these facts with respect to therapeutical potential of hormonal steroids and their synthetic analogues.
- MeSH
- financování organizované MeSH
- gastrointestinální trakt enzymologie metabolismus MeSH
- kůže enzymologie metabolismus MeSH
- lidé MeSH
- nervová tkáň * enzymologie metabolismus MeSH
- statistika jako téma MeSH
- steroidy * izolace a purifikace klasifikace metabolismus MeSH
- tkáně * enzymologie chemie metabolismus MeSH
- tuková tkáň enzymologie metabolismus MeSH
- tukové buňky enzymologie metabolismus MeSH
- Check Tag
- lidé MeSH
