Steroid inhibition of canine ACTH: in vivo evidence for feedback at the corticotrope.
We infused submaximal feedback doses of either dexamethasone (DEX; 0.1 microgram.kg-1.min-1) or corticosterone and cortisol (B+F; 1.5 micrograms.kg-1.min-1) intravenously for 40 min into conscious dogs and measured the adrenocorticotropic hormone (ACTH) responses to hypoglycemia induced by insulin (0.1 U/kg) or to ovine corticotropin-releasing factor (oCRF; 1 microgram/kg); both agents were injected at 120 min. The dose of DEX was chosen to produce suppression of the ACTH response to oCRF equivalent to that produced by B+F. The purpose of the study was to determine 1) whether CRF- and hypoglycemia-induced ACTH secretion are equally inhibited by glucocorticoid treatment and 2) whether DEX and B+F have differential effects in the inhibition of stress-induced ACTH secretion. We found that peak ACTH responses to hypoglycemia and CRF were equally inhibited by DEX (36 +/- 6 and 52 +/- 9%, respectively). The peak ACTH responses to hypoglycemia and CRF were also equally inhibited after B+F infusion (45 +/- 13 and 65 +/- 5%, respectively). There was no significant interaction between the steroid administered and the stimulus given in controlling the ACTH response (by 2-way analysis of variance). The results suggest that pituitary feedback is of primary importance in suppression of canine ACTH secretion by delayed feedback and that the natural and synthetic steroids both act at this site.
Keller-Wood
M
M
Department of Physiology, University of California, San Francisco 94143.
Leeman
E
E
Shinsako
J
J
Dallman
M F
MF
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004285:Dogs; D005246:Feedback; D005260:Female; D006854:Hydrocortisone / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism*; D012016:Reference Values
D007328:Insulin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone; D006854:Hydrocortisone