Glucocorticoids Inhibit Corticotropin-Releasing Factor-Induced Production of Adenosine 3<i>′</i>,5<i>′</i>-Monophosphate in Cultured Anterior Pituitary Cells*

Abstract

The effect of corticotropin-releasing factor (CRF) on ACTH secretion and cAMP production by cultured anterior pituitary cells was investigated. Intracellular cAMP production was stimulated over 13-fold within 10 min in response to 10 nM CRF, reaching a plateau between 20 and 30 min. This was followed by a gradual decline in cellular cAMP, which was associated with its release into the medium. The release of both cAMP and ACTH followed similar time courses and remained linear over a 4-h incubation. CRF caused a dose-dependent increase in both cAMP production and ACTH release over a similar concentration range during short (30-min) incubations when cellular cAMP was maximal. During longer (4-h) incubations, however, significantly higher concentrations of CRF were required to stimulate cAMP production than those needed to stimulate ACTH release. Pretreatment of these cells with 20 nM dexamethasone for 18 h prevented CRF-stimulated ACTH secretion and significantly attenuated cAMP production at all time points during the 4 h. Concentrations of dexamethasone required to prevent CRF-stimulated ACTH release and cAMP production as well as 8-bromo-cAMP-stimulated ACTH release were similar. Equivalent results were obtained with corticosterone. These results suggest that changes in intracellular cAMP levels may, at least in part, mediate the action of CRF on ACTH secretion in the anterior pituitary gland and that one mechanism by which glucocorticoids exert their inhibitory action on corticotrophs may involve an effect on cAMP production.