Suppression of growth hormone (GH) secretion by a selective GH-releasing hormone (GHRH) antagonist : direct evidence for involvement of endogenous GHRH in the generation of GH pulses

• Published in: The Journal of clinical investigation Vol. 92; no. 2; pp. 695 - 701
• Main Authors: JAFFE, C. A, DEMOTT FRIBERG, R, BARKAN, A. L
• Format: Journal Article
• Language: English
• Published: Ann Arbor, MI American Society for Clinical Investigation 01-08-1993
• Subjects: Activity Cycles; Adult; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Growth Hormone - blood; Growth Hormone - secretion; Hormones and neuropeptides. Regulation; Humans; Hypothalamus. Hypophysis. Epiphysis. Urophysis; Kinetics; Male; Sermorelin - analogs & derivatives; Sermorelin - pharmacology; Vertebrates: endocrinology; Human; STH; Peptide hormone; Gonadotropin RH; Neuroendocrine regulation; Male; Hypothalamus; Endocrine secretion; Hypothalamic hormone; Protein hormone; Adenohypophyseal hormone; Pulsatile; Hormonal regulation; Pituitary gland; Hormonal investigation; Hormone releasing factor
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/jci116639

To study the potential involvement of growth hormone-releasing hormone (GHRH) in the generation of growth hormone (GH) pulses in humans we have used a competitive antagonist to the GHRH receptor, (N-Ac-Tyr1,D-Arg2)GHRH(1-29)NH2(GHRH-Ant). Six healthy young men were given a bolus injection of GHRH-Ant 400 micrograms/kg body wt or vehicle at 2200 h and nocturnal GH concentrations were assessed by every 10-min blood sampling until 0800 h. Integrated total and pulsatile GH secretion were suppressed during GHRH-Ant treatment by 40 +/- 6 (SE) % and 75 +/- 5%, respectively. GHRH-Ant suppressed maximum (7.6 +/- 2.2 vs 1.8 +/- 0.5 micrograms/liter; P < 0.001) and mean (3.3 +/- 1.0 vs 1.1 +/- 0.2 micrograms/liter; P = 0.02) GH pulse amplitudes. There was no change in integrated nonpulsatile GH levels, pulse frequency, or interpulse GH concentration. GHRH-Ant 400 micrograms/kg also suppressed the GH responses to intravenous boluses of GHRH 0.33 micrograms/kg given 1, 6, 12, and 24 h later by 95, 81, 59, and 4%, respectively. In five healthy men, the responses to 10-fold larger GHRH boluses (3.3 micrograms/kg) were suppressed by 82 and 0%, 1 and 6 h after GHRH-Ant 400 micrograms/kg, respectively. These studies provide the first direct evidence that endogenous GHRH participates in the generation of spontaneous GH pulses in humans.