Clinical studies with synthetic ovine corticotropin-releasing factor.
Ovine corticotropin-releasing factor (oCRF) stimulates increased plasma immunoreactive adrenocorticotropin (IR-ACTH) and IR-cortisol at threshold, half-maximal, and maximal doses of 0.01-0.03, 0.3-1, and 3-10 micrograms/kg, respectively. Side effects occur with increasing frequency, severity, and duration at doses above 1 microgram/kg. oCRF has a prolonged duration of action, at least in part because of the long circulating half-life of intact oCRF in plasma. Increasing doses of oCRF given in late afternoon progressively diminish the next morning's circadian rise in plasma IR-ACTH in normal subjects, but not in Addisonian patients or subjects receiving metyrapone, indicating that prolonged oCRF-induced hypercortisolemia is the cause. Plasma IR-lipotropins and IR-beta-endorphin rise and fall concomitantly with IR-ACTH after oCRF injection. Arginine vasopressin increases the IR-ACTH response to oCRF fourfold when given simultaneously with oCRF. Cushing's disease patients respond variably, suggesting that oCRF may not be a very useful diagnostic agent in Cushing's syndrome. However, the combination of oCRF with growth hormone-releasing factor, gonadotropin-releasing hormone, and thyrotropin-releasing hormone appears to provide a rapid and useful test of combined anterior pituitary function.
Orth
D N
DN
DeBold
C R
CR
DeCherney
G S
GS
Jackson
R V
RV
Sheldon
W R
WR
Nicholson
W E
WE
Uderman
H
H
Alexander
A N
AN
Island
D P
DP
Rivier
J
J
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001127:Arginine Vasopressin / Q000494:pharmacology; D002940:Circadian Rhythm / Q000187:drug effects; D002986:Clinical Trials as Topic; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D003480:Cushing Syndrome / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004357:Drug Synergism; D004723:Endorphins / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010903:Pituitary Gland, Anterior / Q000187:drug effects; D013997:Time Factors; D001615:beta-Endorphin; D008083:beta-Lipotropin / Q000097:blood
D004723:Endorphins; D001127:Arginine Vasopressin; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D008083:beta-Lipotropin; D006854:Hydrocortisone