Urocortin-1 infusion in normal humans.
Urocortin-1 (Ucn-1), a member of the corticotropin-releasing factor family, has been shown in animal studies to have effects on the pituitary-adrenal axis, the cardiovascular system, circulating neurohormones, and renal function and to suppress appetite. For the first time in man we have evaluated these effects of infused Ucn-1 as well as actions on plasma ghrelin, a hormone known to increase appetite. We also assessed Ucn-1 pharmacokinetics. Eight healthy male volunteers consuming a diet of constant sodium and potassium content received 50 micro g Ucn-1 iv over 1 h in a placebo-controlled, randomized, time-matched, cross-over study. Ucn-1 infusion compared with placebo increased plasma levels of corticotropin [44.6 +/- 7.7 vs. 19.1 +/- 3.2 pg/ml (9.5 +/- 1.7 vs. 4.2 +/- 0.7 pmol/liter); P < 0.001], cortisol [15.6 +/- 1.6 vs. 7.7 +/- 1.4 micro g/dl (432 +/- 43 vs. 213 +/- 40 nmol/liter); P < 0.001], and atrial natriuretic peptide [26.2 +/- 3.4 vs. 21.3 +/- 2.2 pg/ml [8.5 +/- 1.1 vs. 6.9 +/- 0.7 pmol/liter); P = 0.019] while suppressing plasma ghrelin (P = 0.008). No hemodynamic or renal effects were observed at the dose used. The plasma Ucn-1 t(1/2) was 52 min based on a one-compartment model. In conclusion, a brief iv infusion of 50 micro g Ucn-1 stimulates plasma ACTH, cortisol, and atrial natriuretic peptide secretion and suppresses plasma ghrelin in healthy male volunteers. The latter effect might contribute to the anorexic action of Ucn-1.
Christchurch Cardioendocrine Research Group, Christchurch School of Medicine and Health Sciences, University of Otago, Christchurch 8001, New Zealand. mark.davis@chmeds.ac.nz
Mark E
ME
Davis
Chris J
CJ
Pemberton
Timothy G
TG
Yandle
John G
JG
Lainchbury
Miriam T
MT
Rademaker
M Gary
MG
Nicholls
Christopher M
CM
Frampton
A Mark
AM
Richards
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001794:Blood Pressure; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D054439:Ghrelin; D006339:Heart Rate; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007668:Kidney / Q000502:physiology; D008297:Male; D008875:Middle Aged; D036361:Peptide Hormones / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism*; D054832:Urocortins
D054439:Ghrelin; D036361:Peptide Hormones; D054832:Urocortins; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone