Glucocorticoid and estrogen receptors are reduced in mitochondria of lung epithelial cells in asthma.

Mitochondrial glucocorticoid (mtGR) and estrogen (mtER) receptors participate in the coordination of the cell's energy requirement and in the mitochondrial oxidative phosphorylation enzyme (OXPHOS) biosynthesis, affecting reactive oxygen species (ROS) generation and induction of apoptosis. Although activation of mtGR and mtER is known to trigger anti-inflammatory signals, little information exists on the presence of these receptors in lung tissue and their role in respiratory physiology and disease. Using a mouse model of allergic airway inflammation disease and applying confocal microscopy, subcellular fractionation, and Western blot analysis we showed mitochondrial localization of GRα and ERβ in lung tissue.

Glucocorticoids induce mitochondrial gene transcription in HepG2 cells: role of the mitochondrial glucocorticoid receptor.

Glucocorticoids are major regulators of a plethora of cellular functions, acting on target cells through glucocorticoid receptors (GR) and modulation of gene transcription, among other mechanisms. One main site of action of glucocorticoids is the hepatocyte, which responds to the hormonal stimulus with induction of several proteins among them enzymes of oxidative phosphorylation (OXPHOS), both nuclearly and mitochondrially encoded. The induction of OXPHOS is regarded as a result of a nuclear action of the receptor on the respective nuclear genes and on genes encoding mitochondrial transcription factors.

Diet and expression of estrogen alpha and progesterone receptors in malignant mammary tissue.

Estrogen receptor (ER) and/or progesterone receptor (PR) expression has been associated with more favorable breast cancer prognosis. Results on the differential association of diet with ER and/or PR positive and negative tumors have been inconclusive. In a large case-control study conducted in Athens, Greece, we investigated whether diet is associated with the expression of ER-alpha or PR in mammary tumors of 421 women with histologically confirmed breast cancer.

Glucocorticoid receptors and other nuclear transcription factors in mitochondria and possible functions.

The central role of mitochondria in basic physiological processes has rendered this organelle a receiver and integrator of multiple regulatory signals. Steroid and thyroid hormones are major modulators of mitochondrial functions and the question arises as to how these molecules act at the molecular level. The detection in mitochondria of steroid and thyroid hormone receptors suggested their direct action on mitochondrial functions within the context of the organelle.

Diet and expression of estrogen alpha and progesterone receptors in the normal mammary gland.

Objective: It has been recently reported that expression of estrogen alpha (ER-alpha) and progesterone (PR) receptors in the normal mammary gland is inversely associated with breast cancer risk among postmenopausal women. We investigated whether dietary intakes are associated with the expression of ER-alpha and PR receptors in the apparently normal, as opposed to pathological, mammary tissue.

Methods: In a study in Greece, we examined associations of dietary intakes with ER-alpha and PR expression in the adjacent-to-pathological apparently normal mammary tissue of 562 women with either breast cancer (267 women) or BBD (299 women).

Estrogen alpha and progesterone receptor expression in the normal mammary epithelium in relation to breast cancer risk.

Estrogens play a central role in the etiology of breast cancer, and results from observational studies and randomized trials have also implicated progestins. The effects of these hormones in the mammary tissue are exerted through binding with specific receptor proteins in the cell nucleus. It has been proposed that higher estrogen receptor alpha expression in the normal breast epithelium may increase breast cancer risk.

Steroid and thyroid hormone receptors in mitochondria.

Receptors for glucocorticoids, estrogens, androgens, and thyroid hormones have been detected in mitochondria of various cell types by Western blotting, immunofluorescence labeling, confocal microscopy, and immunogold electron microscopy. A role of these receptors in mitochondrial transcription, OXPHOS biosynthesis, and apoptosis is now being revealed. Steroid and thyroid hormones regulate energy production, inducing nuclear and mitochondrial OXPHOS genes by way of cognate receptors.

Nuclear receptors and other nuclear transcription factors in mitochondria: regulatory molecules in a new environment.

The mitochondrion is the major energy generating organelle of the cell and the site of other basic processes, including apoptosis. The mitochondrial functions are performed in concert with other cell compartments and are regulated by various extracellular and intracellular signals. Several nuclear receptors and other nuclear transcription factors, such as NF-kappa B, AP-1, CREB and p53, involved in growth, metabolic and developmental processes, have been detected in mitochondria.

Glucocorticoid receptor isoforms in human hepatocarcinoma HepG2 and SaOS-2 osteosarcoma cells: presence of glucocorticoid receptor alpha in mitochondria and of glucocorticoid receptor beta in nucleoli.

In the context of a possible direct action of glucocorticosteroids on mitochondrial transcription and/or apoptosis by way of cognate mitochondrial receptors, the possible localization of glucocorticoid receptors alpha and beta (GRalpha and GRbeta) in mitochondria was explored in human hepatocarcinoma HepG2 and osteosarcoma SaOS-2 cells, in which glucocorticoids exert an anabolic and apoptotic effect, respectively. In both cell types, GRalpha was detected in mitochondria, in nuclei and in cytosol by immunofluorescence labeling and confocal scanning microscopy, by immunogold electron microscopy and by Western blotting. GRbeta was shown to be almost exclusively restricted to the nucleus of the two cell types, being particularly concentrated in nucleoli, pointing to a solely nuclear role of this receptor isoform and to a possible function in nucleoli related processes.

Tumour-associated trypsin inhibitor, carcinoembryonic antigen and acute-phase reactant proteins CRP and alpha1-antitrypsin in patients with gastrointestinal malignancies.

Objectives: Elevated serum tumour-associated trypsin inhibitor (TATI) levels have been observed in association with malignancy or inflammation. The aim of our study was to evaluate the role of TATI in gastric and colorectal cancer.

Design And Methods: In preoperative serum samples, we measured TATI, carcinoembryonic antigen (CEA), C-reactive protein (CRP) and alpha(1)-antitrypsin (AAT).

The dynamic localization of the glucocorticoid receptor in rat C6 glioma cell mitochondria.

Glucocorticoids modify gene expression via the translocation of receptors from the cytosol to the nucleus following agonist-associated receptor activation. In this study, we have characterized mitochondrial glucocorticoid (GR) localization and associated translocation kinetics in the C6 mouse glioma cell line. Treatment of the cells, which were cultured in steroid-depleted culture medium, with the GR agonist dexamethasone (dex) resulted in a dramatic decrease in mitochondrial GR levels in parallel with those of the cytosolic receptor.

Oligonucleotide sequences similar to transcription factor consensi of nuclear genes are present in the human mitochondrial genome.

Screening the mitochondrial genome for binding sites for known nuclear transcription factors revealed oligonucleotide sequences identical or with over 85% similarity to consensi sequences for twenty-one transcription factors, modulating nuclear genes involved, among others, in cell proliferation, inflammation and synthesis of ribosomal and mitochondrial proteins. Two of these sequences were found in the D-loop, the others dispersed among structural genes for respiratory enzyme subunits, for t-RNAs and for rRNAs. We hypothesize that the transcription factors corresponding to the detected mitochondrial binding sites and the agents controlling the availability of these factors could play a regulatory role in the diverse functions of mitochondria, such as energy production, differentiation and apoptosis.

Application of denaturing gradient gel electrophoresis (DGGE) to screen for mutations of the human glucocorticoid receptor alpha gene (hGRalpha).

Objectives: In a previous publication, we had presented a sensitive method to detect mutations of the segment of the human glucocorticoid receptor alpha (hGRalpha) gene encoding the ligand binding domain (LBD) and part of the DNA binding domain (DBD) of hGRalpha, as several types of glucocorticoid resistance syndromes have been correlated with mutations in the respective nucleotide sequences. However, mutations affecting various regions covering the whole length of hGRalpha are increasingly reported in a variety of disease states. We now present an expanded screening methodology to detect mutations covering the whole length of hGRalpha.

Effects of dexamethasone on K(+)-evoked glutamate release from rat hippocampal slices.

Dexamethasone (DEX) at physiologically elevated (stress) concentration (1 microM) decreased K(+)-evoked glutamate release from rat hippocampal slices under superfusion in the presence of Ca2+. On the contrary 10 microM DEX increased this K(+)-evoked glutamate release while 0.1 microM DEX had no effect.

The effects of steroid hormones on the transcription of genes encoding enzymes of oxidative phosphorylation.

Regulation of energy metabolism is one of the major functions of steroid hormones. In this process, mitochondria, by way of oxidative phosphorylation, play a central role. Depending on the energy needs of the cell, on the tissue, on the developmental stage and on the intensity of the hormonal stimulus, the response can be an activation of pre-existing respiratory chain components, an increased transcription of nuclear-encoded and/or mitochondrial-encoded respiratory chain enzyme (OXPHOS) genes and of biosynthesis of the respective enzyme subunits or, in extreme cases of high energy needs, an increase in the number of mitochondria and mitochondrial DNA content per cell.

Glucocorticoid and thyroid hormone receptors in mitochondria of animal cells.

This article concerns the localization of glucocorticoid and thyroid hormone receptors in mitochondria of animal cells. The receptors are discussed in terms of their potential role in the regulation of mitochondrial transcription and energy production by the oxidative phosphorylation pathway, realized both by nuclear-encoded and mitochondrially encoded enzymes. A brief survey of the role of glucocorticoid and thyroid hormones on energy metabolism is presented, followed by a description of the molecular mode of action of these hormones and of the central role of the receptors in regulation of transcription.

Mitochondrial localization of glucocortocoid receptor in glial (Müller) cells in the salamander retina.

Glucocorticoid hormones regulate the transcription of nuclear genes by way of their receptors. In addition, these hormones modulate mitochondrial gene transcription by mechanisms that remain poorly understood. Using immunofluorescence labeling in isolated Müller and photoreceptor cells and in intact salamander retina, we found that the glucocorticoid receptor (GR) is localized in both cell types.