Steroid hormone receptors represent a major target in drug discovery. As ligand inducible transcription factors, their activity can be modulated by small lipophilic molecules. Here we describe two panels of potent and selective luciferase reporter cell lines based on cells with low endogenous steroid receptor activity (U2OS). The panels contain reporter cell lines for estrogen receptors α and β, androgen, glucocorticoid, mineralocorticoid, and progesterone receptors. In the first panel, the activation of either synthetic, steroid response elements containing promoter or viral promoter is mediated by full-length steroid receptors. The second panel is based on the expression of the chimeric receptor, which was created by the replacement of the N-terminal part of the molecule by Gal4 DBD and that binds to multiple UAS sites in the reporter promoter. Both panels were extensively characterized by profiling 28 ligands in dose response manner in agonist and antagonist mode. We have analyzed and compared the responses to tested ligands from both panels and concluded that in general both systems generated similar qualitative response in terms of potency, efficacy, partial agonism/antagonism, mixed agonistic/antagonistic profiles and the rank of potencies was well conserved between both panels. However, we have also identified some artifacts introduced by the Gal4/LBD reporter assays in contrast to their full-length receptor reporter counterparts. Keeping in mind the advantages and drawbacks of each reporter format, these cell lines represent powerful and selective tools for profiling large compound libraries (HTS) and for detailed study of mechanisms by which compounds exert their biological effects.

• MeSH
• aktivace transkripce * účinky léků   MeSH
• genetické inženýrství metody   MeSH
• knihovny malých molekul analýza   MeSH
• lidé MeSH
• luciferasy genetika   metabolismus   MeSH
• nádorové buněčné linie MeSH
• objevování léků metody   MeSH
• plazmidy genetika   MeSH
• promotorové oblasti (genetika) účinky léků   MeSH
• rekombinantní proteiny genetika   metabolismus   MeSH
• reportérové geny MeSH
• rychlé screeningové testy metody   MeSH
• sekvenční delece MeSH
• steroidní receptory * agonisté   antagonisté a inhibitory   genetika   metabolismus   MeSH
• steroidy farmakologie   MeSH
• transfekce MeSH
• transkripční faktory genetika   metabolismus   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• knihovny malých molekul MeSH
• luciferasy MeSH
• rekombinantní proteiny MeSH
• steroidní receptory * MeSH
• steroidy MeSH
• transkripční faktory MeSH

The aim of current study was to evaluate the effect of the most common anthocyanidins (cyanidin, delphinidin, malvidin, pelargonidin, and peonidin) on the transcriptional activity of steroid and nuclear receptors. The activities of steroid receptors - progesterone receptor (PR), estrogen receptor (ER), androgen receptor (AR), glucocorticoid receptor (GR), and nuclear receptors - vitamin D receptor (VDR), retinoid X receptor (RXR), retinoic acid receptor (RAR), pregnane X receptor (PXR), and thyroid receptor (TR) were assessed using either stable transfected luciferase gene reporter cell lines or transiently transfected cell lines. The cytotoxicity assays and gene reporter assays were performed after the 24-h treatment of cells with increasing range of concentrations (10 nM to 50 µM) of selected anthocyanidins. The results of experiments indicate that none of the examined anthocyanidins in all tested concentrations caused remarkable changes of transcriptional activity of studied steroid receptors, but their increasing concentrations slightly inhibited transcriptional activity of nuclear receptors induced by model agonists.

• Klíčová slova
• Anthocyanidins, nuclear receptors, steroid receptors, transcriptional activity,
• MeSH
• anthokyaniny farmakologie   MeSH
• genetická transkripce účinky léků   MeSH
• lidé MeSH
• nádorové buňky kultivované MeSH
• receptory cytoplazmatické a nukleární genetika   MeSH
• steroidní receptory genetika   MeSH
• viabilita buněk účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• anthokyaniny MeSH
• receptory cytoplazmatické a nukleární MeSH
• steroidní receptory MeSH

The conventional way steroid hormones work through receptors inside cells is widely acknowledged. There are unanswered questions about what happens to the hormone in the end and why there isn't always a strong connection between how much tissue takes up and its biological effects through receptor binding. Steroid hormones can also have non-traditional effects that happen quickly but don't involve entering the cell. Several possible mechanisms for these non-traditional actions include (a) changes in membrane fluidity, (b) steroid hormones acting on receptors on the outer surface of cells, (c) steroid hormones regulating GABAA receptors on cell membranes, and (d) activation of steroid receptors by factors like EGF, IGF-1, and dopamine. Data also suggests that steroid hormones may be inserted into DNA through receptors, acting as transcription factors. These proposed new mechanisms of action should not be seen as challenging the conventional mechanism. Instead, they contribute to a more comprehensive understanding of how hormones work, allowing for rapid, short-term, and prolonged effects to meet the body's physiological needs.

• Klíčová slova
• Cellular mechanism of steroid receptors, Estrogen receptor, Female sexual behavior, Progesterone receptor, Steroid action,
• MeSH
• centrální nervový systém metabolismus   fyziologie   účinky léků   MeSH
• lidé MeSH
• pohlavní steroidní hormony * metabolismus   MeSH
• steroidní receptory metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• pohlavní steroidní hormony * MeSH
• steroidní receptory MeSH

Microbial indoles have been demonstrated as selective or dual agonists and ligands of the pregnane X receptor (PXR) and aryl hydrocarbon receptor (AhR). However, structural determinants of microbial indoles selectivity towards both receptors remain elusive. Here, we studied the effects of existing and newly synthesized derivatives of indole microbial metabolite tryptamine on the activity of AhR and PXR receptors. We show that the elongation of indolyl-3-alkaneamine chain, indole N-methylation and conversion of indolyl-3-alkaneamines to oleamides resulted in a major increase of PXR activity and in parallel loss of AhR activity. Using reporter gene assays, RT-PCR and TR-FRET techniques, we have characterized in detail the activation of PXR by novel indolyl-3-alkanyl-oleamides, 1-methyltryptamine and 1-methyltryptamine-acetamide. As a proof of concept, we demonstrated anti-inflammatory and epithelial barrier-protective activity of lead derivatives in intestinal Caco-2 cells, employing the measurement of expression of pro-inflammatory chemokines, tight junction genes, trans-epithelial electric resistance TEER, and dextran-FITC permeability assay. In conclusion, we show that a subtle chemical modifications of simple microbial indole metabolite tryptamine, leads to substantial changes in AhR and PXR agonist activities.

• Klíčová slova
• Aryl hydrocarbon receptor, Microbial indoles, Pregnane X receptor, Tryptamine,
• MeSH
• Caco-2 buňky MeSH
• indoly farmakologie   MeSH
• lidé MeSH
• pregnanový X receptor genetika   MeSH
• receptory aromatických uhlovodíků * metabolismus   MeSH
• steroidní receptory * metabolismus   MeSH
• tryptaminy farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• indoly MeSH
• pregnanový X receptor MeSH
• receptory aromatických uhlovodíků * MeSH
• steroidní receptory * MeSH
• tryptamine MeSH Prohlížeč
• tryptaminy MeSH

Lyophilized calf uterine cytosol standards were prepared for quality control of estrogen receptor (ER) determination, and lyophilized cytosols and tissue powders were used for quality control of progesterone receptor (PR) analysis. Two series of four samples were analyzed either for ER or PR contents, twice within one month, by 7 laboratories in 5 countries. Coefficient of variation (CV) of the between-laboratory averages assayed in a single run of ER-positive (ER+) and PR-positive (PR+) standards varied from 29.6 to 61.8% and from 32.4 to 76.2%, respectively. All laboratories, with the exception of a single value, could recognize samples of low, medium, an high ER level, as well as a negative sample. Most laboratories evaluated properly also the level of PR samples. The average between-laboratory CV values of protein determination in the relevant standards were 23%.

• MeSH
• chemické techniky analytické normy   MeSH
• cytosol chemie   MeSH
• dextrany MeSH
• dřevěné a živočišné uhlí MeSH
• imunohistochemie MeSH
• mezinárodní spolupráce MeSH
• receptory pro estrogeny analýza   MeSH
• receptory progesteronu analýza   MeSH
• reprodukovatelnost výsledků MeSH
• řízení kvality MeSH
• skot MeSH
• steroidní receptory analýza   MeSH
• uterus ultrastruktura   MeSH
• zvířata MeSH
• Check Tag
• skot MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• dextrany MeSH
• dřevěné a živočišné uhlí MeSH
• receptory pro estrogeny MeSH
• receptory progesteronu MeSH
• steroidní receptory MeSH

There were synthesized new types of ribbon type steroidal dimers derived from three types of steroidal skeletons (cholic acid, etienic acid, estrone) using Cu(I) catalyzed 1, 3-dipolar cycloaddition reaction. Steroid parts of the molecular "ribbons" are linked by heterocyclic moiety, namely by 2,6-bis((1H-1,2,3-triazol-1-yl)-methyl)pyridine. Compounds synthesized possess different cytotoxic and hormone receptor modulating activities.

• MeSH
• androsteny chemie   MeSH
• antagonisté hormonů chemická syntéza   farmakologie   MeSH
• cytotoxiny chemická syntéza   farmakologie   MeSH
• estron chemie   MeSH
• katalýza MeSH
• kyselina cholová chemie   MeSH
• lidé MeSH
• molekulární struktura MeSH
• nádorové buněčné linie MeSH
• pyridiny chemie   MeSH
• steroidní receptory antagonisté a inhibitory   metabolismus   MeSH
• steroidy chemická syntéza   farmakologie   MeSH
• viabilita buněk účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• androsteny MeSH
• antagonisté hormonů MeSH
• cytotoxiny MeSH
• estron MeSH
• etienic acid MeSH Prohlížeč
• kyselina cholová MeSH
• pyridiny MeSH
• steroidní receptory MeSH
• steroidy MeSH

Structure-activity relationship analysis and profiling of a library of AB-functionalized cholestane derivatives closely related to brassinosteroids (BRs) were performed to examine their antiproliferative activities and activities on steroid hormone receptors. Some of the compounds were found to have strong cytotoxic activity in several human normal and cancer cell lines. The presence of a 3-hydroxy or 3-oxo group and 2,3-vicinal diol or 3,4-vicinal diol moiety were found to be necessary for optimum biological activity, as well as a six-membered B ring. According to the profiling of all steroid receptors in both agonist and antagonist mode, the majority of the cholestanes were weakly active or inactive compared to the natural ligands. Estrogenic activity was detected for two compounds, two compounds possessed antagonistic properties on estrogen receptors and seven compounds showed agonistic activity. Two active cholestane derivatives were shown to strongly influence cell viability, proliferation, cell cycle distribution, apoptosis and molecular pathways responsible for these processes in hormone-sensitive/insensitive (MCF7/MDA-MB-468) breast cancer cell lines.

• Klíčová slova
• Antiproliferative activity, Apoptosis, Cell cycle, Cholestane derivatives, Steroid receptor, Structure-activity relationship,
• MeSH
• apoptóza MeSH
• buněčný cyklus účinky léků   MeSH
• cholestany chemie   farmakologie   MeSH
• inhibiční koncentrace 50 MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• protinádorové látky chemie   farmakologie   MeSH
• screeningové testy protinádorových léčiv MeSH
• steroidní receptory metabolismus   MeSH
• viabilita buněk MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cholestany MeSH
• protinádorové látky MeSH
• steroidní receptory MeSH

As a promiscuous xenobiotic sensor, pregnane X receptor (PXR) plays a crucial role in drug metabolism. Since dietary phytochemicals exhibit the potential to modulate human PXR, this review aims to summarize the plant-derived PXR modulators, including agonists, partial agonists, and antagonists. The crystal structures of the apo and ligand-bound forms of PXR especially that of PXR complexed with binary mixtures are summarized, in order to provide the structural basis for PXR binding promiscuity and synergistic activation of PXR by composite ligands. Furthermore, this review summarizes the characterized agonists, partial agonists, and antagonists of human PXR from botanical source. Contrary to PXR agonists, there are only a few antagonists obtained from botanical source due to the promiscuity of PXR. It is worth noting that trans-resveratrol and a series of methylindoles have been identified as partial agonists of PXR, both in activating PXR function, but also inhibiting the effect of other PXR agonists. Since antagonizing PXR function plays a crucial role in the prevention of drug-drug interactions and improvement of therapeutic efficacy, further research is necessary to screen more plant-derived PXR antagonists in the future. In summary, this review may contribute to understanding the roles of phytochemicals in food-drug and herb-drug interactions.

• Klíčová slova
• Agonists, antagonists, dietary phytochemicals, pregnane X receptor,
• MeSH
• fytonutrienty farmakologie   MeSH
• lidé MeSH
• pregnanový X receptor MeSH
• resveratrol MeSH
• steroidní receptory * chemie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• fytonutrienty MeSH
• pregnanový X receptor MeSH
• resveratrol MeSH
• steroidní receptory * MeSH

The membrane cholesterol was found to bind and modulate the function of several G-protein coupled receptors including muscarinic acetylcholine receptors. We investigated the binding of 20 steroidal compounds including neurosteroids and steroid hormones to muscarinic receptors. Corticosterone, progesterone and some neurosteroids bound to muscarinic receptors with the affinity of 100 nM or greater. We established a structure-activity relationship for steroid-based allosteric modulators of muscarinic receptors. Further, we show that corticosterone and progesterone allosterically modulate the functional response of muscarinic receptors to acetylcholine at physiologically relevant concentrations. It can play a role in stress control or in pregnancy, conditions where levels of these hormones dramatically oscillate. Allosteric modulation of muscarinic receptors via the cholesterol-binding site represents a new pharmacological approach at diseases associated with altered cholinergic signalling.

• Klíčová slova
• Allosteric modulation, Muscarinic receptor, Neurosteroid, Steroid hormone,
• MeSH
• acetylcholin metabolismus   MeSH
• alosterická regulace MeSH
• hormony kůry nadledvin metabolismus   MeSH
• kortikosteron metabolismus   MeSH
• křečci praví MeSH
• kultivované buňky MeSH
• lidé MeSH
• neurosteroidy metabolismus   MeSH
• pohlavní steroidní hormony metabolismus   MeSH
• progesteron metabolismus   MeSH
• receptory muskarinové metabolismus   MeSH
• zvířata MeSH
• Check Tag
• křečci praví MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetylcholin MeSH
• hormony kůry nadledvin MeSH
• kortikosteron MeSH
• neurosteroidy MeSH
• pohlavní steroidní hormony MeSH
• progesteron MeSH
• receptory muskarinové MeSH

Molecular changes associated with malignancy are extremely complex. Early epigenetic events occurring in the common tumor types such as breast or prostate cancer might determine the subsequent genetic changes leading to tumor development and progression. Covalent modifications of histones play a major role as determiners of epigenetic information and are important in the regulation of gene expression. Acetylation generally correlates with transcriptional activation, while methylation can signal either activation or repression. However, little is known about the interplay of different epigenetic events. Steroid hormones regulate many cellular processes through signal transduction pathways that result in a variety of post-translational modifications. Such modifications can be triggered by steroid hormones in cooperation with coactivators(p160 family proteins, CBP, p300, p/CAF) and/or corepressors (N-Cor, SMRT, TZF). There is still much to learn about their regulation and the molecular and physiological consequences of these modifications.

• MeSH
• acetylace MeSH
• histony metabolismus   MeSH
• lidé MeSH
• metylace MeSH
• pohlavní steroidní hormony metabolismus   MeSH
• signální transdukce fyziologie   MeSH
• steroidní receptory metabolismus   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• histony MeSH
• pohlavní steroidní hormony MeSH
• steroidní receptory MeSH