Isolated pituitary cells: glucocorticoids do not rapidly suppress ACTH secretion in response to CRF.
The possibility of a direct rapid suppressive effect of glucocorticoids on stimulated adrenocorticotropic hormone (ACTH) release was investigated in perifused normal pituitary cells attached to microcarriers. Forty-eight hours after attachment to Cytodex beads, cells were transferred to two columns (one experimental, one control), perifused at a rate of 300-350 microliters/min, and equilibrated for 3 h. Either rat or ovine corticotropin-releasing factor (CRF; 2 nM) were used to stimulate ACTH release, and fractions collected every 5 min were assayed for immunoreactive ACTH. Concomitant treatment with CRF and glucocorticoids (dexamethasone 100 nM or corticosterone 1 microM), or glucocorticoid pretreatment for up to 2 h, did not affect the release of ACTH occasioned by repetitive 5-min exposures to CRF at 30-min intervals. In addition, when ovine CRF was given as two 30-min infusions 1 h apart, neither concomitant steroid administration nor steroid pretreatment for 90 min affected the release of ACTH compared with controls. The lack of rapid steroid inhibition was not an artifact of enzymatic dispersion or microcarrier attachment, since no rapid inhibitory response was seen with acutely perifused rat anterior pituitary quarters. We thus conclude that in vitro rapid inhibitory effects of glucocorticoids on ACTH release do not occur at the level of the pituitary. Accordingly such action in vivo presumably reflects acute steroid-induced effects on the hypothalamus or higher centers.
Familari
M
M
Medical Research Centre, Prince Henry's Hospital, Melbourne, Australia.
Funder
J W
JW
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D003911:Dextrans; D005938:Glucocorticoids / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008863:Microspheres; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D003911:Dextrans; D005938:Glucocorticoids; C052839:Cytodex; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone