Disease relevance of xGR

• We report here that a protein of relative molecular mass 19,000 (Mr = 19 K) encompassing the DNA-binding domain of the glucocorticoid receptor that has been overexpressed in Escherichia coli and purified to homogeneity reversibly ligates two Zn(II) or Cd(II) ions [1].
• The glucocorticoid receptor precludes the binding of a transcriptional repressor protein to the long terminal repeat of the mouse mammary tumor virus [2].

High impact information on xGR

• The glucocorticoid receptor enhances or represses transcription by binding to specific DNA sequences termed glucocorticoid response elements, or GREs [1].
• In vivo footprinting demonstrated agonist- and RU486-induced GR binding to its DNA response element (GRE), while the other antagonist, RU43044, did not promote GR-GRE interaction [3].
• Addition of dexamethasone, which binds to the glucocorticoid receptor and releases Xbra, causes formation of mesoderm [4].
• We show here that dexamethasone upregulates transcription and expression of the serum- and glucocorticoid-inducible kinase 1 (SGK1) in insulin-secreting cells, an effect reversed by mifepristone (RU486), an antagonist of the nuclear glucocorticoid receptor [5].
• A glucocorticoid analogue, triamcinolone acetonide (TA), is injected into Xenopus laevis oocytes that express an exogeneous glucocorticoid receptor (GR) [6].

Biological context of xGR

• These results provide the first evidence that expression of the GR gene is regulated during early embryonic development [7].
• To study the possible role of the glucocorticoid receptor (GR) in early embryogenesis, we isolated a Xenopus glucocorticoid receptor cDNA from an embryonic stage 17 cDNA library [7].
• Thus, the A alpha and B beta genes are probably regulated at least in part by direct transcriptional activation by glucocorticoid-receptor complexes [8].
• Although the ERE shares some structural features with the glucocorticoid responsive element (GRE) it is distinct from this element since it neither binds glucocorticoid receptor in vitro nor does it confer glucocorticoid inducibility to a fusion gene [9].
• Mutagenesis of either of the two main FoxA binding sites showed that the distal site, -232/-221, conferred FoxA1-dependent partial inhibition of glucocorticoid receptor (GR) driven MMTV transcription [10].

Anatomical context of xGR

• Overexpression of this Xenopus GR in COS cells confers the ability to transactivate a GRE-tk CAT promoter construct in a ligand dependent manner [7].
• Unliganded GR is located in the cytosol and hormone triggers its nuclear translocation and association with the chromatin fibers [11].
• AFM imaging revealed accumulation of macromolecules matching the size of GR at the nuclear envelope beginning 5 min after glucocorticoid hormone injection [12].
• To better understand the roles of corticosteroids in amphibian metamorphosis we analyzed the developmental and hormone-dependent expression of glucocorticoid receptor (GR) mRNA in the brain (diencephalon), intestine and tail of Xenopus laevis tadpoles [13].
• These observations suggest that thyroid and ovarian hormones exert an influence on glucocorticoid receptor capacity and may belong to the factors which regulate glucocorticoid receptors [14].

Associations of xGR with chemical compounds

• We show that microinjection of RNA for MyoD fused to the ligand-binding domain of either the estrogen or glucocorticoid receptor results in hormone-dependent activation of MyoD function, as assayed by ectopic induction of muscle-specific actin mRNA [15].
• CHIF messenger RNA showed up-regulation by both mineralocorticoid and glucocorticoid receptor agonists in the distal colon, which was not diminished by cycloheximide [16].
• The level of GR mRNA was increased by treatment with CORT in the intestine but not in the brain or tail [13].
• 100 mM molybdate lowers the apparent affinity of the receptor for [3H]dexamethasone, suggesting that molybdate can interact with the X. laevis glucocorticoid receptor [17].
• The synergy of CORT with T(3) on tadpole tail resorption may depend on the accelerated accumulation of GR transcripts in this tissue during metamorphosis, which may be driven by rising plasma thyroid hormone titers [13].

Analytical, diagnostic and therapeutic context of xGR

• Expression of the Xenopus GR gene at the RNA level was analyzed by Northern blot hybridization [7].
• In parallel, western blot analysis showed accumulation of GR over the same time scale after glucocorticoid hormone stimulation [12].

References