Urocortin-1 Infusion in Normal Humans

• Published in: The journal of clinical endocrinology and metabolism 2004-03, Vol.89 (3), p.1402-1409
• Main Authors: Davis, Mark E., Pemberton, Chris J., Yandle, Timothy G., Lainchbury, John G., Rademaker, Miriam T., Nicholls, M. Gary, Frampton, Christopher M., Richards, A. Mark
• Format: Article
• Language: English
• Subjects: Adrenocorticotropic Hormone - blood; Adult; Biological and medical sciences; Blood Pressure; Corticotropin-Releasing Hormone - administration & dosage; Corticotropin-Releasing Hormone - pharmacokinetics; Cross-Over Studies; Endocrinopathies; Fundamental and applied biological sciences. Psychology; Ghrelin; Heart Rate; Humans; Hydrocortisone - blood; Kidney - physiology; Male; Medical sciences; Middle Aged; Peptide Hormones - metabolism; Pituitary Gland, Anterior - drug effects; Pituitary Gland, Anterior - metabolism; Urocortins; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2003-031231

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 μg 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 μg/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 t1/2 was 52 min based on a one-compartment model. In conclusion, a brief iv infusion of 50 μg 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.