| |
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.
|
|