Glucocorticoid inhibition of stimulus-evoked adrenocorticotrophin release caused by suppression of intracellular calcium signals.
Stress provokes a cohort of homeostatic reflexes by the central nervous, the immune as well as the metabolic control systems of the body. These powerful adaptive responses, which can cause a collapse of body homeostasis in the absence of feedback inhibition, are suppressed by adrenal glucocorticoid hormones. A prominent and physiologically significant early action of glucocorticoids that requires the induction of newly synthesized messenger RNA and protein is the suppression of ACTH release by anterior pituitary corticotroph cells. It is demonstrated here that glucocorticoids inhibit stimulated ACTH secretion in pituitary corticotroph tumour (AtT-20) cells by reducing stimulus-evoked intracellular free calcium transients. Thus, the data show for the first time that intracellular calcium signals may be modified by rapidly induced proteins. It is proposed that this is a general mechanism that underlies the early inhibitory effects of glucocorticoids during stress in various types of cell.
Antoni
F A
FA
Department of Pharmacology, University of Edinburgh, U.K.
Hoyland
J
J
Woods
M D
MD
Mason
W T
WT
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002460:Cell Line; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000502:physiology*; D051379:Mice; D010903:Pituitary Gland, Anterior / Q000378:metabolism
D005938:Glucocorticoids; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D002118:Calcium