Time dependent effects of glucocorticoids on adrenocorticotropin secretion of 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 exposure to glucocorticoids and glucocorticoid concentration has been investigated. CRF-stimulated ACTH secretion of perifused rat pituitary fragments was measured 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 with 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 after incubation for 1 min at concentrations between 10(-8) and 10(-6) M. The same absolute quantity of the glucocorticoids produced no inhibition when incubation was prolonged to 50 min or when a lower concentration was used. Immediately after the perifusion stimulation of ACTH secretion was observed. The results suggest the possibility of minimizing the side effects of glucocorticoids by prolonging drug release.
Bruns
R
R
Institute of Pharmaceutical Chemistry, Westfälische-Wilhelms-Universität Münster, Germany.
Rohdewald
P
P
D000287:Administration, Topical; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D019540:Area Under Curve; D019819:Budesonide / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000187:drug effects* / Q000494:pharmacology; D005446:Fluocinolone Acetonide / Q000031:analogs & derivatives / Q000494:pharmacology; D000068298:Fluticasone; D005938:Glucocorticoids / Q000494:pharmacology*; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D011239:Prednisolone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D005446:Fluocinolone Acetonide; D019819:Budesonide; C007734:flunisolide; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D011239:Prednisolone; D000068298:Fluticasone