Stimulation of cyclic AMP accumulation and corticotropin release by synthetic ovine corticotropin-releasing factor in rat anterior pituitary cells: site of glucocorticoid action.

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Abstract
A 2.5-fold stimulation of cAMP cellular content is measured 60 s after addition of 100 nM synthetic ovine corticotropin-releasing factor (C-RF; corticoliberin) to rat anterior pituitary cells in culture. A maximal response of cAMP content at 400% above control is observed between 2 and 30 min after addition of the peptide, whereas an 8-fold stimulation of cAMP released into the incubation medium is measured between 10 and 180 min. A linear 7-fold increase of ACTH release is observed for up to 3 h. Preincubation for 18 h with the potent glucocorticoid dexamethasone has no effect on C-RF-induced cAMP accumulation. The same treatment with dexamethasone causes an 80% inhibition of ACTH release induced by both C-RF and the cAMP derivative 8-bromoacAMP. Ovine C-RF is a potent stimulator of cAMP accumulation in rat anterior pituitary cells and the process is insensitive to the action of dexamethasone. The marked inhibition by dexamethasone of ACTH secretion induced by a cAMP derivative indicates that glucocorticoids exert their potent inhibitory effect on ACTH secretion at a step distant to cAMP formation.