Time dependent effects of glucocorticoids on adrenocorticotropin secretionof rat pituitaries ex-vivo

Different glucocorticoids have been compared with respect to the inhibition of corticotropin-releasing factor (CRF)-mediated adrenocorticotropin (ACTH ) secretion from pituitary fragments of the rat. The influence of time of e xposure to glucocorticoids and glucocorticoid concentration has been invest igated. CRF-stimulated ACTH secretion of perifused rat pituitary fragments was meas ured by a chemiluminescence immunoassay. ACTH secretion was monitored over three days. Inhibition of CRF-stimulated ACTH secretion by glucocorticoids was quantified by the area under the curve of CRF-stimulated ACTH secretion over baseline. Concentrations needed to inhibit ACTH secretion decreased w ith the receptor affinities of the glucocorticoids as follows: fluticasone propionate; receptor affinity 1800, concentration 10(-8) M; budesonide, 935 and 3-2.5 x 10(-8) M; flunisolide, 478 and 5 x 10(-7) M; prednisolone, 10 and 10(-6) M. CRF-stimulated secretion was inhibited by glucocorticoids aft er incubation for 1 min at concentrations between 10(-8) and 10(-6) M. The same absolute quantity of the glucocorticoids produced no inhibition when i ncubation was prolonged to 50 min or when a lower concentration was used. I mmediately after the perifusion stimulation of ACTH secretion was observed. The results suggest the possibility of minimizing the side effects of gluco corticoids by prolonging drug release.