Changes In Nuclear Volume Research Articles

Rethinking nuclear shaping: insights from the nuclear drop model.

Changes in the nuclear shape caused by cellular shape changes are generally assumed to reflect an elastic deformation from a spherical nuclear shape. Recent evidence, however, suggests that the nuclear lamina, which forms the outer nuclear surface together with the nuclear envelope, possesses more area than that of a sphere of the same volume. This excess area manifests as folds/wrinkles in the nuclear surface in rounded cells and allows facile nuclear flattening during cell spreading without any changes in nuclear volume or surface area. When the lamina becomes smooth and taut, it is inextensible, and supports a surface tension. At this point, it is possible to mathematically calculate the limiting nuclear shape purely based on geometric considerations. In this paper, we provide a commentary on the "nuclear drop model" which seeks to integrate the above features. We outline its testable physical properties and explore its biological implications.

Integer topological defects organize stresses driving tissue morphogenesis.

Tissues acquire function and shape via differentiation and morphogenesis. Both processes are driven by coordinating cellular forces and shapes at the tissue scale, but general principles governing this interplay remain to be discovered. Here, we report that self-organization of myoblasts around integer topological defects, namely spirals and asters, suffices to establish complex multicellular architectures. In particular, these arrangements can trigger localized cell differentiation or, alternatively, when differentiation is inhibited, they can drive the growth of swirling protrusions. Both localized differentiation and growth of cellular vortices require specific stress patterns. By analyzing the experimental velocity and orientational fields through active gel theory, we show that integer topological defects can generate force gradients that concentrate compressive stresses. We reveal these gradients by assessing spatial changes in nuclear volume and deformations of elastic pillars. Altogether, we propose integer topological defects as mechanical organizing centers controlling differentiation and morphogenesis.

Mesoscale phase separation of chromatin in the nucleus.

Intact-organism imaging of Drosophila larvae reveals and quantifies chromatin-aqueous phase separation. The chromatin can be organized near the lamina layer of the nuclear envelope, conventionally fill the nucleus, be organized centrally, or as a wetting droplet. These transitions are controlled by changes in nuclear volume and the interaction of chromatin with the lamina (part of the nuclear envelope) at the nuclear periphery. Using a simple polymeric model that includes the key features of chromatin self-attraction and its binding to the lamina, we demonstrate theoretically that it is the competition of these two effects that determines the mode of chromatin distribution. The qualitative trends as well as the composition profiles obtained in our simulations compare well with the observed intact-organism imaging and quantification. Since the simulations contain only a small number of physical variables we can identify the generic mechanisms underlying the changes in the observed phase separations.

Striatal Atrophy and Hypometabolism in Drug-Resistant Non-Ketotic Hyperglycemic Chorea-Ballism.

Non-ketotic hyperglycemic chorea-ballism (NKHCB) is a rare movement disorder associated with poorly controlled type-2 diabetes,1 in the majority of cases characterized by: unilateral hemicorea-hemiballism, contralateral striatum hyperintensity on T1-weighted magnetic resonance imaging (MRI), and clinical and radiological improvement after blood glucose correction.2 Herein, we present a case of NKHCB with following evidence of striatal atrophy. A 56-year-old woman presented to the emergency department of another hospital because of sudden onset of involuntary movements of the left limbs attenuated during rest. She had a recent history of type-2 diabetes mellitus treated with poor glycemic control. A computed tomography scan showed striatal hyperdensity. Routine laboratory findings were normal, despite a fasting blood glucose level of 167 mg/dL and glycate hemoglobin level of 130 mmol/mol (14%). MRI scan showed striatal T1-weighted hyperintensity with a corresponding hyperintensity in T2-weighted (Fig. 1A and B) and fluid attenuated inversion recovery (FLAIR) scans. The patient was diagnosed with NKHCB. Glucose control was optimized and anti-choreic therapy was started with haloperidol 5 mg/day and tetrabenazine 25 mg/day with a slight clinical benefit. The patient arrived at our attention 4 months after symptom onset for diagnostic re-evaluation. The motor impairment persisted and involuntary movements worsened insidiously. The neurological examination showed choreoatetosic and ballic movements of the left body side. Involuntary movements increased with distraction maneuvers and resolved during rest at bed. Blood fasting glucose was 126 mg/dL and glycated hemoglobin was 62 mmol/mol (7.8%). MRI scan showed the resolution of the striatal alteration, but highlighted atrophic evolution (Fig. 1C and D). A fluorodeoxyglucose positron emission tomography scan showed an intense hypometabolism consistent with morphological MRI atrophy findings (Fig. 1E and F). Haloperidol was discontinued and clinical improvement was obtained with tetrabenazine 25 mg thrice/day, piracetam 3 g/day and topiramate 25 mg twice/day. The comparison of MRI volumes at the two timepoints showed, on the right side, a decrease in caudate head and putamen volumes and an increase in the lateral ventricle volume. The two main pathophysiological mechanisms proposed for NKHCB are related to metabolic dysfunction and to microvascular damage.3, 4 Our findings may be explained by irreversible metabolic or vascular damage. The microvascular hypothesis might explain the prevalent unilateral clinical onset. The prognostic implication of our observation is related to the high variability in outcomes.1 Extended lesions at MRI were associated with prolonged involuntary movements.5 Our findings of focal atrophy strengthen these results, suggesting a role of the pathological disease severity, in-vivo assessed by MRI, to determine the persistence of the disorder. We hypothesize that a mild disorder, solved with anti-chorea treatment, might be associated with a lower degree of atrophy, unrecognized without a volumetric analysis. In conclusion, our case of NKHCB showed focal striatal atrophy and hypometabolism after radiological resolution in a 4-month follow-up, associated with poor response to glucose-control and anti-chorea treatment. To date, for the first time we documented nuclear volume changes with a quantitative approach demonstrating irreversible pathological changes in NKHCB, explaining drug-resistant cases. (1) Research project: A. Conception, B. Organization, C. Execution. (2) Statistical Analysis: A. Design, B. Execution, C: Review and Critique. (3) Manuscript: A. Writing of the first draft, B. Review and Critique. P.G.S.: 1A, 1B, 1C, 2A, 2B, 3A F.A.: 1A, 1B, 2C, 3B N.A.: 1C, 3B M.A.V.: 1A, 1B, 1C, 2C, 3B M.F.: 1A, 1B, 2C, 3B This study has been approved by the Ethics Committee of IRCCS San Raffaele Hospital and has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The patient provided written informed consent to be anonymously included in this report. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. No funding was received for this work and the authors have no conflicts of interest to report. P.G. Scamarcia, N. Anzalone, and M.A. Volontè have nothing to disclose. F. Agosta is Section Editor of NeuroImage: Clinical; has received speaker honoraria from Philips, Novartis and Biogen Idec; and receives or has received research supports from the Italian Ministry of Health, AriSLA (Fondazione Italiana di Ricerca per la SLA), and the European Research Council. M. Filippi is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

Mesoscale Phase Separation of Chromatin in the Nucleus

Intact-organism imaging of Drosophila larvae reveals and quantifies chromatin-aqueous phase separation. The chromatin can be organized near the lamina layer of the nuclear envelope, conventionally fill the nucleus, be organized centrally, or as a wetting droplet. These transitions are controlled by changes in nuclear volume and the interaction of chromatin with the lamina (part of the nuclear envelope) at the nuclear periphery. Using a simple polymeric model that includes the key features of chromatin self-attraction and its binding to the lamina, we demonstrate theoretically that it is the competition of these two effects that determines the mode of chromatin distribution.

Mesoscale Phase Separation of Chromatin in the Nucleus

Intact-organism imaging of Drosophila larvae reveals and quantifies chromatin-aqueous phase separation. The chromatin can be organized near the lamina layer of the nuclear envelope, conventionally fill the nucleus, be organized centrally, or as a wetting droplet. These transitions are controlled by changes in nuclear volume and the interaction of chromatin with the lamina (part of the nuclear envelope) at the nuclear periphery. Using a simple polymeric model that includes the key features of chromatin self-attraction and its binding to the lamina, we demonstrate theoretically that it is the competition of these two effects that determines the mode of chromatin distribution. The qualitative trends as well as the compositional profiles obtained in our simulations compare well with the observed intact-organism imaging and quantification. Since the simulations contain only a small number of physical variables we can identify the generic mechanisms underlying the changes in the observed phase separations.

The nucleoporin ELYS regulates nuclear size by controlling NPC number and nuclear import capacity.

How intracellular organelles acquire their characteristic sizes is a fundamental question in cell biology. Given stereotypical changes in nuclear size in cancer, it is important to understand the mechanisms that control nuclear size in human cells. Using a high-throughput imaging RNAi screen, we identify and mechanistically characterize ELYS, a nucleoporin required for post-mitotic nuclear pore complex (NPC) assembly, as a determinant of nuclear size in mammalian cells. ELYS knockdown results in small nuclei, reduced nuclear lamin B2 localization, lower NPC density, and decreased nuclear import. Increasing nuclear import by importin α overexpression rescues nuclear size and lamin B2 import, while inhibiting importin α/β-mediated nuclear import decreases nuclear size. Conversely, ELYS overexpression increases nuclear size, enriches nuclear lamin B2 at the nuclear periphery, and elevates NPC density and nuclear import. Consistent with these observations, knockdown or inhibition of exportin 1 increases nuclear size. Thus, we identify ELYS as a novel positive effector of mammalian nuclear size and propose that nuclear size is sensitive to NPC density and nuclear import capacity.

Nuclear size changes caused by local motion of cell boundaries unfold the nuclear lamina and dilate chromatin and intranuclear bodies.

The mechanisms by which mammalian nuclear shape and size are established in cells, and become abnormal in disease states are not understood. Here, we tracked motile cells that underwent systematic changes in cell morphology as they moved from 1-D to 2-D micro-patterned adhesive domains. Motion of the cell boundaries during cell motility caused a dynamic and systematic change in nuclear volume. Short time scales (∼1 h) distinguished the dilation of the nucleus from the familiar increase that occurs during the cell cycle. Nuclear volume was systematically different between cells cultured in 3-D, 2-D and 1-D environments. Dilation of the nuclear volume was accompanied by dilation of chromatin, a decrease in the number of folds in the nuclear lamina, and an increase in nucleolar volume. Treatment of 2-D cells with non-muscle myosin-II inhibitors decreased cell volume, and proportionately caused a decrease in nuclear volume. These data suggest that nuclear size changes during cell migration may potentially impact gene expression through the modulation of intranuclear structure.

Cell micropatterning reveals the modulatory effect of cell shape on proliferation through intracellular calcium transients

The mechanism by which cell shape regulates the function of the cell is one of the most important biological issues, but it remains unclear. Here, we investigated the effect of the regulation of cell shape on proliferation by using a micropatterning approach to confine MC3T3-E1 cells into specific shapes. Our results show that the proliferation rate for rectangle-, triangle-, square- and circle-shaped osteoblasts increased sequentially and was related to the nuclear shape index (NSI) but not the cell shape index (CSI). Interestingly, intracellular calcium transients also displayed different patterns, with the number of Ca2+ peaks increasing with the NSI in shaped cells. Further causal investigation revealed that the gene expression levels of the inositol 1,4,5-triphosphate receptor 1 (IP3R1) and sarco/endoplasmic reticulum Ca2+-ATPase 2 (SERCA2), two major calcium cycling proteins in the endoplasmic reticulum (ER), were increased with an increase in NSI as a result of nuclear volume changes. Moreover, the down-regulation of IP3R1 and/or SERCA2 using shRNAs in circle-shaped or control osteoblasts resulted in changes in intracellular calcium transient patterns and cell proliferation rates towards that of smaller-NSI-shaped cells. Our results indicate that changes in cell shape changed nuclear morphology and then the gene expression of IP3R1 and SERCA2, which produced different intracellular calcium transient patterns. The patterns of intracellular calcium transients then determined the proliferation rate of the shaped osteoblasts.

A novel multiplexed, image-based approach to detect phenotypes that underlie chromosome instability in human cells.

Chromosome instability (CIN) is characterized by a progressive change in chromosome numbers. It is a characteristic common to virtually all tumor types, and is commonly observed in highly aggressive and drug resistant tumors. Despite this information, the majority of human CIN genes have yet to be elucidated. In this study, we developed and validated a multiplexed, image-based screen capable of detecting three different phenotypes associated with CIN. Large-scale chromosome content changes were detected by quantifying changes in nuclear volumes following RNAi-based gene silencing. Using a DsRED-LacI reporter system to fluorescently label chromosome 11 within a human fibrosarcoma cell line, we were able to detect deviations from the expected number of two foci per nucleus (one focus/labelled chromosome) that occurred following CIN gene silencing. Finally, micronucleus enumeration was performed, as an increase in micronucleus formation is a classic hallmark of CIN. To validate the ability of each assay to detect phenotypes that underlie CIN, we silenced the established CIN gene, SMC1A. Following SMC1A silencing we detected an increase in nuclear volumes, a decrease in the number of nuclei harboring two DsRED-LacI foci, and an increase in micronucleus formation relative to controls (untreated and siGAPDH). Similar results were obtained in an unrelated human fibroblast cell line. The results of this study indicate that each assay is capable of detecting CIN-associated phenotypes, and can be utilized in future experiments to uncover novel human CIN genes, which will provide novel insight into the pathogenesis of cancer.

Unique Mechanical Properties of Cell Nuclei Regulated by Chromatin

Nuclear mechanics and structure could affect gene regulation and gene expression. Chromatin, a major component of cell nuclei, could play an important role in maintaining nuclear integrity and their mechanical properties. Previous studies on nuclear mechanical properties have focused largely on the role of the nuclear lamina, using techniques such as AFM and micropipette aspiration. In this work, we explicitly address the contributions of chromatin to nuclear rheology after isolation from the cell using a microfluidic optical stretcher. We find that isolated nuclei swell in volume under uni-axial stress and exhibit significant softening with increased nuclear size, which can be described by a filtration model for the nuclear membrane and a cortical chromatin model, respectively. In addition, changes to the state of chromatin condensation via histone modifications or chromatin remodeling processes (ATP, topoisomerase II) can strongly impact nuclear morphology and compliance. Moreover, isolated nuclear mechanics is also sensitive to ionic conditions: nuclei stiffen with increasing ionic strength of the buffer and exhibit a transition from stretch to contraction in the presence of multivalent ions (only). Finally, we find that in contrast to other studies suggesting a high refractive index of cell nuclei compared to the cytoplasm, the refractive index of isolated cell nuclei of a variety of cell types can be lower than the refractive index of the cells. The presented work establishes a quantitative link between nuclear mechanical properties and the compaction state of chromatin, which can be modulated by a change in nuclear volume, chromatin remodeling or electrochemical environment.

Nuclear field shift effect in isotope fractionation of thallium

Environmental transport of Tl is affected by redox reaction between Tl(I) and Tl(III) and ligand exchange reactions of them. In order to deepen the knowledge of Tl chemistry, we investigated fractionation of Tl stable isotopes (203Tl and 205Tl) in a chemical exchange system. Tl isotopes were fractionated in a liquid–liquid extraction system, in which aqueous and organic phases are hydrochloric acid solution and dichloroethane including a crown ether, respectively. After purification by ion-exchange chemistry, the isotope ratio of 205Tl/203Tl in equilibrated aqueous phase was measured precisely by multiple-collector–inductively-coupled-plasma–mass-spectrometry. A large isotope fractionation >1 ‰ was found. Electronic structures of possible Tl species (hydrated Tl+, Tl3+, and Tl chlorides) were calculated by ab initio methods, and the isotope fractionation factor was theoretically obtained. The isotope fractionation via intramolecular vibrations was calculated to be much smaller than the experimental result. The isotope fractionation via isotopic change in nuclear volume, named the nuclear field shift effect, was calculated to be >1 ‰ in Tl(I)–Tl(III) redox systems and/or ligand exchange systems of Tl(III). The nuclear field shift effect was found to be the major origin of Tl isotope fractionation.

Morphological Gill Analysis of Fish Species Prochilodus Lineatus after Exposure to Pollutants

The gill is the respiratory organ in fish but it is also responsible for ion exchange with the environment, what makes it highly susceptible to pollutants. This study aimed to identify possible histological and histochemical changes in the gill of fish species Prochilodus lineatus exposed to biodegradable detergents and water from an urban lake. The results showed not only morphological alterations such as lamellae fusion and hyperplasia, as well as increase in collagen, changes in nuclear volume and increase in the number of chloride and mucous cells. These results show that common pollutants dumped into rivers and urban lakes can cause several changes in the respiratory organ, possibly leading to a metabolic deficit in fish.

Fine control of nuclear confinement identifies a threshold deformation leading to lamina rupture and induction of specific genes

The quest to understand how the mechanical and geometrical environment of cells impacts their behavior and fate has been a major force driving the recent development of new technologies in cell biology research. Despite rapid advances in this field, many challenges remain in order to bridge the gap between the classical and simple cell culture plate and the biological reality of actual tissue. In tissues, cells have their physical space constrained by neighboring cells and the extracellular matrix. Here, we propose a simple and versatile device to precisely and dynamically control this confinement parameter in cultured cells. We show that there is a precise threshold deformation above which the nuclear lamina breaks and reconstructs, whereas nuclear volume changes. We also show that different nuclear deformations correlate with the expression of specific sets of genes, including nuclear factors and classical mechanotransduction pathways. This versatile device thus enables the precise control of cell and nuclear deformation by confinement and the correlative study of the associated molecular events.

Fluorescence spectroscopy ofH-rastransfected murine fibroblasts: A comparison with Monte Carlo simulations

Autofluorescence properties of tissues have been widely used to diagnose various types of malignancies. In this study, we measured the autofluorescence properties of H-ras transfected murine fibroblasts and the counterpart control cells. The pair of cells is genetically identical except for the transfected H-ras gene. We applied Monte Carlo simulations to evaluate the relative contributions of Rayleigh and Mie scattering effects towards fluorescence in an in vitro model system of normal and H-ras transfected fibroblasts. The experimental results showed that fluorescence emission intensity was higher for normal cells than the malignant counterpart cells by about 30%. In normal cells, linearity in emission intensity was observed for cell densities of up to 1.0 x 10(6) cells/ml whereas for transformed cells it was up to 1.4 x 10(6) cells/ml. Nuclear volume changes give good account for the differences in the intrinsic fluorescence between normal and malignant cells. The Monte Carlo (MC) code, newly developed for this study, explains both predominant experimental features: the large fluorescence intensity differences between the transfected and the corresponding control cells as well as the phenomena of the red shift in the excitation spectra as a function of cell density. The contribution of Rayleigh scattering was found to be predominant compared to Mie scattering.

Nucleic acids absorbance in Mid IR and its effect on diagnostic variates during cell division: A case study with lymphoblastic cells

The differences in the absorbance in the mid infrared region (Mid IR) between normal and abnormal tissues have been shown to be a possible criterion for the detection of different forms of cancer. The present work aimed to study the effects of cell growth and DNA synthesis on the RNA/DNA ratio, which is a promising parameter for cancer diagnosis by inducing synthesis of DNA. Lymphoblastic cell lines were synchronized by methotrexate and harvested for Fourier transform infrared microscopy (FTIR-MSP) at 30-min interval after thymidine addition. The distribution of DNA in the cells/nuclei and variation of nuclear size was studied using the fluorescent dye propidium iodide (PI) and the nuclear volume was calculated from microscopy. We analyzed the ratio of RNA and DNA to quantify the relative amounts during the process by taking the ratios I(1121)/I(1020) (symmetric) and the I(1244)/I(1230) (antisymmetric) phosphate vibrations. The pattern of changes in the ratios overtime obtained in the symmetric and antisymmetric vibrations were similar though the magnitudes were different. Only a minor effect on the RNA/DNA ratio (due to nuclear volume changes) was observed. The effect due to the unfolding of DNA is greatly masked due to RNA absorbance. The effectiveness of this ratio may lie in the increased transcriptional levels in carcinogenic tissues rather than changes occurring due to unfolding and folding of DNA.

Static Compression of Single Chondrocytes Catabolically Modifies Single-Cell Gene Expression

Previous work has established that mechanical forces can lead to quantifiable alterations in cell function. However, how forces change gene expression in a single cell and the mechanisms of force transmission to the nucleus are poorly understood. Here we demonstrate that the gene expression of proteins related to the extracellular matrix in single articular chondrocytes is modified by compressive forces in a dosage-dependent manner. Increasing force exposure catabolically shifts single-cell mRNA levels of aggrecan, collagen IIa, and tissue inhibitor of metalloproteinase-1. Cytohistochemistry reveals that the majority of strain experienced by the cell is also experienced by the nucleus, resulting in considerable changes in nuclear volume and structure. Transforming growth factor- β1 and insulin-like growth factor-I offer mechanoprotection and recovery of gene expression of aggrecan and metalloproteinase-1. These results suggest that forces directly influence gene transcription and may do so by changing chromatin conformation.

Relationship between petal abscission and programmed cell death in Prunus yedoensis and Delphinium belladonna.

Depending on the species, the end of flower life span is characterized by petal wilting or by abscission of petals that are still fully turgid. Wilting at the end of petal life is due to programmed cell death (PCD). It is not known whether the abscission of turgid petals is preceded by PCD. We studied some parameters that indicate PCD: chromatin condensation, a decrease in nuclear diameter, DNA fragmentation, and DNA content per nucleus, using Prunus yedoensis and Delphiniumbelladonna which both show abscission of turgid petals at the end of floral life. No DNA degradation, no chromatin condensation, and no change in nuclear volume was observed in P. yedoensis petals, prior to abscission. In abscising D.belladonna petals, in contrast, considerable DNA degradation was found, chromatin was condensed and the nuclear volume considerably reduced. Following abscission, the nuclear area in both species drastically increased, and the chromatin became unevenly distributed. Similar chromatin changes were observed after dehydration (24 h at 60°C) of petals severed at the time of flower opening, and in dehydrated petals of Ipomoea nil and Petunia hybrida, severed at the time of flower opening. In these flowers the petal life span is terminated by wilting rather than abscission. It is concluded that the abscission of turgid petals in D. belladonna was preceded by a number of PCD indicators, whereas no such evidence for PCD was found at the time of P. yedoensis petal abscission. Dehydration of the petal cells, after abscission, was associated with a remarkable nuclear morphology which was also found in younger petals subjected to dehydration. This nuclear morphology has apparently not been described previously, for any organism.

Studies on nuclear degeneration during programmed cell death of synergid and antipodal cells in Triticum aestivum

Morphological changes in the nuclear degeneration of the synergid (mainly the synergid that receives the pollen tube) and antipodal cells in Triticum aestivum were studied. Although located in the same embryo sac, and derived from the same megaspore, nuclear degeneration of the synergid and antipodal cells differs greatly. Nuclear degeneration in the synergid is characterized by pycnosis, i.e., total chromatin condensation, nuclear deformation and distinct shrinkage in volume, followed by the formation of an irregular and densely stained mass—the degenerated nucleus—while the nucleolus disappears prior to the degradation of chromatin. In contrast, in the nuclear degeneration of antipodal cells, chromatin is only partly condensed and the nuclear volume changes only slightly after the distinct chromatin condensation. Chromatolysis then occurs, i.e., stainable contents disappear while the nuclear envelope is retained. The nucleoli persist after the disappearance of the chromatin. The possible functions of nuclear degeneration of synergid and antipodal cells are discussed, especially with respect to the guidance of pollen tube growth and the proliferation of free-nuclear endosperm. The degeneration of synergids and antipodal cells in T. aestivum are distinct forms of programmed cell death, regarded as cytoplasmic cell death and nuclear degradation in advance of cell death, respectively.

Transient permeability leak of nuclear envelope induced by aldosterone.

The mineralocorticoid hormone aldosterone controls fluid and electrolyte transport in target cells of the kidney and the cardiovascular system. Classic genomic aldosterone action involves the activation of cytosolic mineralocorticoid receptors and translocation into the cell nucleus where specific transcription processes are initiated. A key barrier of the intracellular signalling pathway is the nuclear envelope, which physically separates the nucleoplasm from the cytoplasm. It was shown recently that aldosterone changes ion conductivity of the nuclear envelope mediated by nuclear pore complexes. The latter are supramolecular nanomachines responsible for import and export of inorganic ions and macromolecules. The aim of the present study was to test whether aldosterone changes the macromolecule permeability of the nuclear envelope. Aldosterone-responsive Xenopus laevis oocytes were used as a model system. We isolated the cell nuclei at defined times after hormone injection. By means of confocal fluorescence microscopy and fluorescence-labelled dextrans we evaluated passive macromolecule import and export in isolated nuclei. 10 minutes after aldosterone injection nuclear envelope permeability of 10 kD dextran was found sharply increased. At the same time cell nuclei were found swollen by about 28%. Changes in nuclear volume and nuclear envelope permeability lasted 5 to 15 minutes and could be inhibited by the mineralocorticoid receptor blocker spironolactone. We conclude that aldosterone transiently changes the barrier function of the nuclear envelope. This short-lasting permeability change signals the start of a sustained transcription process that follows in response to steroids.