Corticosteroids penetrate cells and bind to a high affinity cytoplasmic receptor protein → a structural change occurs in the steroid receptor complex that allows its migration into the nucleus and binding to glucocorticoid response elements (GRE) on the chromatin → transcription of specific mRNA → regulation of protein synthesis
MECHANISM OF ACTION AT CELLULAR LEVEL
Corticosteroids
penetrate cells and bind to a high affinity cytoplasmic receptor protein → a structural change
occurs in the steroid receptor complex that allows its migration into the
nucleus and binding to glucocorticoid response elements (GRE) on the chromatin → transcription of
specific mRNA → regulation of protein
synthesis. This process
takes at least 30–60 min : effects of corticosteroid are not immediate, and
once the appropriate proteins are synthesized—effects persist much longer than
the steroid itself. In many tissues, the overall effect is catabolic, i.e.
inhibition of protein synthesis. This may be a consequence of steroid directed
synthesis of an inhibitory protein.
The
glucocorticoid receptor (GR) is very widely distributed (in practically all
cells). It has been cloned and its structure determined; made up of ~ 800 amino
acids.
Several
coactivators and corepressors modulate the interaction of liganded GR with the GREs,
altering the intensity of response.
Because
the GR largely maintains uniformity throughout the body, tissue specificity is
not exhibited by different glucocorticoids, and all members produce the same
constellation of effects.
The
functional scheme of glucocorticoid receptor is presented in Fig. 4.9. Direct
evidence of gene expression mediated action has been obtained for actions
listed in the box.
Some
actions of corticoids are exerted more rapidly (like inhibition of ACTH release
from pituitary). These may be mediated by a cell membrane receptor or a
different mechanism not involving protein synthesis.
Related Topics
TH 2019 - 2024 pharmacy180.com; Developed by Therithal info.