Understanding glucocorticoids


The glucocorticoid hormone system plays an important role in glucose regulation, as well as carbohydrate, lipid and protein metabolism. It helps regulate immune, circulatory and renal function. Additionally, the glucocorticoid system influences growth (including weight regulation), development, bone metabolism and central nervous system activity.

Key components of the system are glucocorticoid hormones, the glucocorticoid receptor (GR), and the hormone-receptor complex formed when glucocorticoid binds with GR.

Glucocorticoid enters the cell and binds with the GR. This hormone-receptor complex then enters the cell nucleus and turns on specific genes by binding with DNA and directing the transcription process.

from Kaltreider et al:

Glucocorticoids induce numerous cellular and physiological effects that are mediated predominantly through their interaction with the cytosolic steroid hormone receptor GR. GR, a member of the nuclear receptor superfamily, mediates glucose homeostasis, immune modulation, cellular growth and differentiation, and numerous other physiological responses in a wide variety of tissues. Unlike many other sex steroid receptors that are localized predominantly to the nucleus, GR is normally sequestered in a preactive state in the cytosol, bound in a complex that includes multiple heat shock proteins (HSP56, 70, and 90). Upon steroid binding, GR conformation is altered, unmasking a nuclear localization signaling motif and a DNA-binding domain. This leads to the translocation of the ligand-bound GR to the nucleus in a form that can interact with DNA. Once in the nucleus, GR binds as a homodimer in a head-to-head manner to its cis-acting DNA recognition element, the GRE (consensus GRE half-site, TGTTCT). GR also has been shown to participate through protein-protein interactions with other cofactors (co-activators/co-repressors), leading to either positive or negative effects on transcription of specific glucocorticoid-responsive genes.