Methotrexate regulates the expression of glucocorticoid receptor alpha and beta isoforms in normal human peripheral mononuclear cells and human lymphocyte cell lines in vitro

Goecke, I. Annelise; Álvarez, Claudio; Henríquez, Juan Pablo; Salas, Karime; Molina, María Luisa; Ferreira, Arturo; Gatica, H

doi:10.1016/j.molimm.2006.07.303

Cited by 37 publications

(28 citation statements)

References 41 publications

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“…21 The content of a and b GR messenger RNA (mRNA) was determined by using human 18S transcript from each complementary DNA sample as an internal standard and normalizing the results.…”

Section: Gr Assay In Pbmcmentioning

confidence: 99%

Increased Expression of the Glucocorticoid Receptor β in Infants With RSV Bronchiolitis

Díaz

Pinto²,

Mamani³

et al. 2012

Pediatrics

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“…21 The content of a and b GR messenger RNA (mRNA) was determined by using human 18S transcript from each complementary DNA sample as an internal standard and normalizing the results.…”

Section: Gr Assay In Pbmcmentioning

confidence: 99%

Increased Expression of the Glucocorticoid Receptor β in Infants With RSV Bronchiolitis

Díaz

Pinto²,

Mamani³

et al. 2012

Pediatrics

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“…It was also shown that β isoform of GR can become dominant after treatment of the cells by pro inflammatory cytokines TNFα and IL1, and it can be a mechanism for development of insensitivity to glucocorticoid hormones (Webster et al, 2001). On the contrary, agents increasing the relative expression level of α isoform (e.g., methotrexate, widely used to treat autoimmune diseases and inflammation) increases the sensitivity of cells to glucocorticoids (Goecke et al, 2007). A high level of GRβ is observed in some patients with insensitivity to the hormone therapy forms of asthma, rheumatoid arthritis, sys temic lupus erythematosus, acute lymphoblastoid leu kemia, etc.…”

Section: Merkulov Merkulovamentioning

confidence: 99%

Glucocorticoid receptor isoforms generated by alternative splicing and alternative translation initiation

Меркулов

Меркулова

2012

Russ J Genet Appl Res

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The glucocorticoid hormone receptor (NR3C1) is the transcription factor that controls a large variety of physiological processes in mammals. According to modern estimates, the glucocorticoid receptor participates in regulation of the expression of thousands of genes; however, the sets of glucocorticoid con trolled genes in different cell types are different. At the same time the amplitude, directivity, and time and dose dependence of the hormone response are broadly variable both for the same gene in different cell types and for different genes in the same cell. Such specificity of a glucocorticoid receptor is determined, on the one hand, by architecture of regulatory regions of target genes, and on the other hand, by the complexity of the glucocorticoid receptor gene. The gene has nine alternative promoters and produces numerous protein isoforms as a result of alternative splicing and alternative translation initiation. This review summarizes the current knowledge on glucocorticoids receptor isoforms and mechanisms of their formation.

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“…Levels of GRβ are also elevated in glucocorticoid resistant forms of asthma, rheumatoid arthritis, ulcerative colitis, nasal polyposis, systemic lupus erythematosus, acute lymphoblastic leukemia, and chronic lymphocytic leukemia [129][130][131][132][133][134][135][136][137]. Interestingly, methotrexate, an effective drug for treating autoimmune and inflammatory diseases, has been reported to selectively increase GRα at the expense of GRβ thereby improving glucocorticoid sensitivity of lymphocytes [138]. The molecular basis for altered expression of GRβ is not known but recent work has implicated the possible involvement of the alternative splicing factor serine-arginine rich protein p30c (SRp30c) [139].…”

Section: Splice Variant Grβmentioning

confidence: 99%

The Glucocorticoid Receptor

Oakley

Cidlowski

2010

Nuclear Receptors

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Abstract:Glucocorticoids are essential for life and play critical roles in many diverse physiological processes including metabolism, development, growth, inflammation, and apoptosis. Drugs that mimic the actions of glucocorticoids are widely used to treat diseases such as cancer, inflammation, and autoimmune disorders. The effects of glucocorticoids and their synthetic derivatives are mediated by the glucocorticoid receptor (GR, NR3C1), a member of the nuclear receptor superfamily of ligand-dependent transcription factors. Upon binding hormone, the GR translocates into the nucleus where it regulates gene expression by direct binding to DNA and/or through interactions with other transcription factors. The GR is derived from a single gene, yet recent work has demonstrated that alternative processing of this gene generates an astonishing array of GR isoforms with unique expression, functional, and gene regulatory profiles. Here, we discuss the molecular and cellular mechanisms of GR signaling, and the potential role for GR isoforms in regulating the specificity and sensitivity of glucocorticoid responsiveness in healthy and diseased tissues. INTRODUCTIONGlucocorticoids are endogenous hormones essential for life that are released by the adrenal cortex in a circadian manner and in response to stress. The secretion of these hormones is under control of the hypothalamic-pituitary-adrenal (HPA) axis. In response to physical or emotional stress, the hypothalamus releases corticotrophin releasing hormone (CRH) which acts on the anterior pituitary to stimulate the synthesis and secretion of adrenocorticotropin hormone (ACTH). ACTH then acts on the adrenal cortex to stimulate the production and secretion of glucocorticoids. Only about 10% of circulating glucocorticoid is free, as the majority of the hormone is transported in the blood bound to corticosteroid binding globulin. Glucocorticoids act on nearly all tissues and cells to regulate many diverse physiological processes that function to maintain homeostasis in the face of stressful perturbations. Named for their metabolic effects converting proteins and lipids into glucose during times of low blood sugar, glucocorticoids also play critical roles in immune 63

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Methotrexate regulates the expression of glucocorticoid receptor alpha and beta isoforms in normal human peripheral mononuclear cells and human lymphocyte cell lines in vitro

Cited by 37 publications

References 41 publications

Increased Expression of the Glucocorticoid Receptor β in Infants With RSV Bronchiolitis

Increased Expression of the Glucocorticoid Receptor β in Infants With RSV Bronchiolitis

Glucocorticoid receptor isoforms generated by alternative splicing and alternative translation initiation

The Glucocorticoid Receptor

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