Table 3.

GC-mediated molecular mechanisms involved in reducing GRα expression.

Level of regulation	Molecular mechanism	Species	GRα mRNA expression	GRα protein expression	References
Epigenetic	DNA methylation of GRα gene • Rodents: exon 17 • Humans: exon 1F, exon 1C, exon 1B, exon 1H, exon 1D	Rodent Human	Reduced Reduced	Reduced Reduced	(30, 32, 33, 42)(24, 25, 81, 92)
Transcriptional	GRα gene regulation via nGREa • Present in exon 6	Human	Reduced	N.Db	(107)
Post-transcriptional	miRNA • Rodents: miR-96, miR-101a, miR-142-3p, miR-433, miR-29b, miR-340-5p, miR-18 and miR-124a • Humans: miR-124, miR-130b and miR-142-3p	Rodent Human	Reduced Reduced	Reduced Reduced	(38, 40, 42, 127, 128, 129)(84, 89, 95, 130)
Post-translational	Phosphorylation • Rodents:  ◦ Multiple mouse mutations(Ser212, Ser220 and Ser234)  ◦ Hyper-phosphorylation at Ser412 • Humans: hyper-phosphorylation at Ser211, Ser226 and Ser404	Mouse Human	N.Ac N.A	Decreased Decreased	(136, 137)(135, 136)
	Ubiquitination • Rodents: K426 • Humans: K419 Proteasome degradation (i.e. use of proteasome inhibitors) • Rodents: MG132 or bortezomib (BZ) • Humans: MG132 or BZ	Mouse Human Mouse Human	N.A N.A N.A N.A	Decreased Decreased Decreased Decreased	(99, 104, 105, 139, 142)(105, 141, 143, 144, 145, 146)(99, 104, 105, 139, 142)(105, 141, 143, 144, 145, 146)
	Sumoylation • Specific site unknown	Human	N.A	Decreased	(152)

^aNegative glucocorticoid response element (nGRE), ^bNot detected (N.D), ^cNot applicable (N.A) as effects exerted on GRα protein.