Urocortin-1 infusion in normal humans

Area of Science:

• Endocrinology
• Neuroendocrinology
• Cardiovascular Physiology

Background:

• Urocortin-1 (Ucn-1), a CRF-family peptide, exhibits diverse physiological effects in animal models.
• Potential roles in the pituitary-adrenal axis, cardiovascular function, and appetite regulation are suggested.
• Human studies are needed to confirm Ucn-1's effects and explore its impact on appetite-related hormones like ghrelin.

Purpose of the Study:

• To investigate the effects of intravenous Ucn-1 infusion in humans for the first time.
• To evaluate Ucn-1's impact on the pituitary-adrenal axis, cardiovascular system, and renal function.
• To assess Ucn-1's influence on plasma ghrelin levels and its pharmacokinetic profile.

Main Methods:

• A placebo-controlled, randomized, crossover study involving eight healthy male volunteers.
• Administration of 50 micro g Ucn-1 intravenously over 1 hour.
• Measurement of plasma levels of ACTH, cortisol, atrial natriuretic peptide, ghrelin, and assessment of hemodynamic and renal parameters.

Main Results:

• Ucn-1 infusion significantly increased plasma ACTH, cortisol, and atrial natriuretic peptide levels compared to placebo.
• Plasma ghrelin levels were significantly suppressed following Ucn-1 infusion.
• No significant hemodynamic or renal effects were observed at the studied dose.
• The plasma Ucn-1 half-life (t1/2) was determined to be 52 minutes.

Conclusions:

• Intravenous Ucn-1 administration stimulates ACTH, cortisol, and atrial natriuretic peptide secretion in healthy men.
• Ucn-1 effectively suppresses plasma ghrelin, a key appetite-stimulating hormone.
• These findings suggest that Ucn-1's anorexic effects may be mediated, in part, by ghrelin suppression.