Early glucocorticoid induction of calmodulin and its suppression by corticotropin-releasing factor in pituitary corticotrope tumor (AtT20) cells.
Glucocorticoids inhibit stimulus-evoked ACTH secretion by the rapid induction of new protein(s) that suppress intracellular free calcium signals. The present study examined whether the calcium receptor protein, calmodulin, is induced by glucocorticoids in the mouse pituitary corticotrope tumor (AtT20 D16:16) cell line. Treatment of AtT20 D16:16 cells with the synthetic glucocorticoid dexamethasone markedly (up to 10-fold) increased the level of a single (approximately 1.6kb) calmodulin mRNA 90 min after the application of steroid. Puromycin applied 15 min before and during dexamethasone treatment blocked the induction of this mRNA, suggesting that additional glucocorticoid induced transcription factor proteins may be required for enhanced calmodulin gene transcription. A two-fold increase in the intensity of an approximately 18K immunoreactive calmodulin protein band was detected by immunoblotting at 90 min after dexamethasone administration. Corticotropin releasing factor, added for 30 min at the start of steroid treatment, prevented the increase of calmodulin mRNA, as well as the suppression of corticotropin releasing factor-evoked ACTH release caused by dexamethasone. These data suggest that calmodulin may be involved in the early phase of glucocorticoid inhibition of pituitary ACTH release.
Shipston
M J
MJ
Department of Pharmacology, University of Edinburgh, U.K.
Antoni
F A
FA
D000324:Adrenocorticotropic Hormone / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D002147:Calmodulin / Q000096:biosynthesis* / Q000235:genetics* / Q000302:isolation & purification; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007700:Kinetics; D010911:Pituitary Neoplasms; D011691:Puromycin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D002147:Calmodulin; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011691:Puromycin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone