The interaction of corticotropinreleasing factor (CRF) preparations, dexamethasone and actinomycin D (Act D) on ACTH release from the rat pituitary was studied in vivo and in vitro. In in vivo studies, ACTH release, as indicated by plasma corticosterone levels, following iv injection of the crude rat pituitary stalk and median eminence (SME) extracts or a purified porcine hypothalamic CRF, was considerably suppressed by pretreatment of the rat with 400 μg/100 g body wt of dexamethasone ip. One hundred μg Act D/100 g body wt injected ip before, but not after, dexamethasone prevented the dexamethasone suppression of the action of these CRF preparations. In in vitro experiments, rat pituitaries released a considerable amount of ACTH into the incubation medium when 0.4–0.8 rat SME was added to the medium. When the pituitaries were preincubated with 2–20 μg/ml of dexamethasone for 2 hr, the amount of ACTH released by SME was greatly reduced. Preincubation with Act D, 0.5–2 μg/ml, also decreased SME-induced ACTH release, but the extent of suppression was smaller than that due to dexamethasone. Either dexamethasone or Act D added together with SME during the incubation period caused only a slight suppression of ACTH release. On the other hand, when the pituitaries were preincubated with dexamethasone and Act D together, the amount of ACTH released by SME was significantly larger than when the pituitaries were preincubated with dexamethasone only. This suggests that dexamethasone blockade was prevented with Act D. After the dexamethasone blockade was established, Act D added simultaneously with SME did not reverse this blockade. Thus, in vitro studies are in good agreement with the in vivo results. Act D reduced in vitro pituitary RNA synthesis measured by incorporation of 3H-uridine, and protein synthesis measured by 14C-leucine incorporation by 83 and 23%, respectively. Addition of dexamethasone to the medium did not significantly influence the effects of Act D. Prevention of dexamethasone suppression of SME-induced ACTH release by Act D and the suppressive effect of Act D itself were completely eliminated by adding excess denatured DNA into the medium along with Act D. The following conclusions were drawn: 1) Dexamethasone suppresses the action of CRF at the pituitary level, 2) this dexamethasone blockade does not develop immediately, 3) dexamethasoneblockade of CRF requires a process which involves DNA-dependent RNA synthesis, and 4) the process of ACTH release by CRF does not require RNA synthesis. (Endocrinology85: 300, 1969)
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Arimura et al. (1969) studied this question.