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SUMMARY
[3H]Oestradiol-17β binding by cytoplasmic and nuclear fractions of human uterine tissue homogenates was studied by intact tissue and cell-free incubation techniques. In the absence of divalent cations, swelling and rupture of endometrial nuclei led to a loss of nuclear receptor complex into the cytoplasmic fraction of the homogenate. Divalent cations at a concentration of 0·003 mol/l, however, caused precipitation of the cytoplasmic receptor complex, inhibited [3H]oestradiol-17β binding by the cytoplasmic receptor and inhibited the extraction of soluble nuclear receptor complex. These effects were minimal when 0·001 m-magnesium ions were added to the sucrose—tris buffer. Studies of the distribution of oestrogen receptors in homogenates of human uterine tissue in 0·001 m-magnesium—sucrose—tris buffer revealed the presence of a soluble and an insoluble nuclear receptor complex. More of the nuclear receptor complex was obtained in the soluble form when the incubation temperature was raised from 25 to 37 °C. Evidence is presented for the transfer of [3H]oestradiol-17β from the cytoplasmic to the nuclear fractions by a temperature-dependent process and for the binding of [3H]oestradiol-17β by nuclear receptors in the absence of the cytoplasmic fraction.
Department of Biochemistry, Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong SAR, China
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Department of Biochemistry, Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong SAR, China
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Department of Biochemistry, Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong SAR, China
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Department of Biochemistry, Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong SAR, China
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Department of Biochemistry, Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong SAR, China
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association of coactivator dysfunction with multiple human disease states, including neurodegeneration, malignancies and metabolic disorders. The nuclear receptor coactivator p300 functions to assemble multimolecular transcriptional regulatory protein
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. The gene-set also contains nuclear receptors of known and unknown functions and a limited selection of genes encoding pro-/anti-inflammatory mediators. Here we apply this microarray to analyse RNA from primary HOSE cell cultures, with and without prior
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AP-HP Hôpital Pitié-Salpêtrière-Charles Foix, Nutrition Department, Paris, France
AP-HP Hôpital Pitié-Salpêtrière-Charles Foix, Diabetology-Metabolism Department, Paris, France
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AP-HP Hôpital Pitié-Salpêtrière-Charles Foix, Nutrition Department, Paris, France
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Introduction HNF-4 belongs to the nuclear receptor superfamily, and in mammals two paralog genes encode the HNF-4α and HNF-4γ forms. HNF-4α is expressed in the liver, kidney, pancreas and intestine ( Benoit et al. 2006 ). Numerous studies
Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands
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Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Centre, Leiden, The Netherlands
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Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Centre, Leiden, The Netherlands
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Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Centre, Leiden, The Netherlands
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Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Centre, Leiden, The Netherlands
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Department of Vascular Medicine, Amsterdam Diabetes Centre, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
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Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands
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Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Centre, Leiden, The Netherlands
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Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Centre, Leiden, The Netherlands
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Bledsoe RK Chandra G Consler TG Kliewer SA Stimmel JB Willson TM Zavacki AM Moore DD . 1999 Bile acids: natural ligands for an orphan nuclear receptor . Science 284 1365 – 1368 . https://doi.org/10.1126/science.284.5418.1365 10.1126/science.284
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inhibitor sunitinib, which is a substrate of CYP3A4, was rapidly metabolized in patients treated with mitotane. However, the precise mechanism of CYP3A4 induction by mitotane is not well understood. The orphan nuclear receptor (NR), steroid and xenobiotic
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Introduction
Nuclear receptors
The cell's long-term response to environmental stimuli is associated with changes in cellular proliferation, differentiation and metabolism mediated by the modification of the protein content of a cell via differential gene expression. Transcription factors that regulate the activity of specific genes receive such stimuli in different ways. Peptide hormones, growth factors and neurotransmitters bind and activate cell surface receptors, initiating a cascade of intracellular signals by a complex system of secondary messengers that leads to the activation of transcription factors. Other transcription factors that are responsive to steroid and thyroid hormones, retinoids and other signalling molecules belong to the distinct class of nuclear receptors present in the cytoplasm or nucleus. Direct and high affinity binding of a specific signalling molecule or ligand activates the nuclear receptors to exert control on the rate of transcription of target genes via interaction with specific DNA sequences
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Dias M Bernardi Videira N Bruder M Amorim Amato A Migliorini Figueira AC 2019 Modulation of nuclear receptor function: targeting the protein-DNA interface . Molecular and Cellular Endocrinology 484 1 – 14 . ( https://doi.org/10.1016/j
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The measurement of oestrogen receptors in the nuclei of cells of human breast cancer is becoming increasingly important for patient management. However, the steroid-binding properties of the oestrogen nuclear receptor of human cells under different conditions of temperature and ionic strength have received little attention despite the relevance of the receptor for interpretation of assay data. This paper reports a study on the influence of temperature and ionic strength on the exchange rate of [3H]oestradiol from human breast and endometrial nuclear receptor.
When the oestrogen–nuclear receptor complex was bound to intact or sheared nuclei, the displacement of bound [3H]oestradiol into buffer containing excess unlabelled oestradiol increased with temperature but was significant over 24 h even at 4 °C for nuclei from both breast and endometrium. The use of protease inhibitors combined with relabelling of nuclear receptor after incubation confirmed that the observations at 4 °C represented exchange of hormone rather than degradation of the hormone–receptor complex. Degradation was seen at higher temperatures.
Measurement of the on-rate of [3H]oestradiol onto nuclear receptor prefilled with unlabelled oestradiol showed that on-rate was also significant over 24 h at 4 °C The displacement of oestradiol from salt-extracted, hydroxylapatite-precipitated receptor also increased with temperature although, in this case, no displacement could be detected until temperatures above 4 °C were reached.
Only 40% of total oestrogen receptor detectable in intact human nuclei was solubilized by the standard method of salt extraction in 0·6 mol KC1/1. As the salt concentration was raised (0–0·6 mol KC1/1), an increase in the stripping of oestradiol from the hormone–receptor complex was observed. Such stripping of nuclear receptor during salt extraction would lead to a false impression of the proportion of 'empty' nuclear receptors.
The results show that filled oestrogen nuclear receptor from human tumour tissue may be assayed by exchange at 4 °C over 24 h. This eliminates the protease degradation of receptor which occurs at higher assay temperatures.
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received daily injections of 3-MA for 5 days (0.1 ml of 5 mM solution in PBS). *0.01< P <0.05; ** P <0.01. Classical nuclear receptor is involved in the suppression of autophagic regulation by E 2 and P 4 To examine whether hormonal regulation of
