Growth hormone (GH) secretion in active acromegaly after the combined administration of GH-releasing hormone and GH-releasing peptide-6.
His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (called GHRP-6) is a synthetic compound that releases GH in a dose-related, specific, and nonspecies-specific manner, through mechanisms different from those of GHRH. Being, normally, more potent than GHRH, GHRP-6 shows a striking synergistic action when administered simultaneously with GHRH, although the mechanisms and point of action of such a potentiating effect are unknown. The aim of the present study was 2-fold: 1) to further characterize the actions and mechanisms of GHRP-6 as well as its synergistic effects, and 2) to study its actions in acromegalic patients. Eleven acromegalic patients and 12 normal subjects, age and sex matched as controls, underwent 3 tests each on separate occasions, being challenged with GHRH (100 micrograms, iv), GHRP-6 (90 micrograms, iv), or GHRH plus GHRP-6. GH was analyzed as the area under the curve (mean +/- SE; micrograms per L/120 min). In normal subjects, GH secretion was 686 +/- 227 after GHRH, 1787 +/- 510 after GHRP-6, and 4111 +/- 671 after GHRH plus GHRP-6; the level of GH secreted after GHRH plus GHRP-6 treatment was significantly (P < 0.05) higher than the arithmetic sum of GH levels after both compounds administered separately. In acromegalic patients, the level of GH secreted after GHRH was 1468 +/- 499, that after GHRP-6 was 2595 +/- 762, and that after GHRH plus GHRP-6 was 4949 +/- 1043; this last value was not significantly different from the arithmetical addition of levels produced by both compounds administered separately. These results indicate that GH-secreting pituitary adenomas respond surprisingly well to either GHRH or GHRP-6 despite being deprived for long periods (even years) of the physiological regulation exerted by the hypothalamus. In addition, the synergistic action of GHRH plus GHRP-6 was observed in normal subjects, but not in acromegalic patients. These results suggest that GHRP-6 does not need to operate through hypothalamic factors to exert its GH-releasing action, even for eliciting a greater response than GHRH. On the other hand, the synergistic effect of GHRH plus GHRP-6 appears to need the cooperation of the hypothalamus, but how this occurs is still undetermined.
Popovic
V
V
Institute of Endocrinology, University Clinical Center, Belgrade, Yugoslavia.
Damjanovic
S
S
Micic
D
D
Petakov
M
M
Dieguez
C
C
Casanueva
F F
FF
D000172:Acromegaly / Q000503:physiopathology*; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D004357:Drug Synergism; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage; D006801:Humans; D007031:Hypothalamus / Q000503:physiopathology; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology
D009842:Oligopeptides; C041048:growth hormone releasing hexapeptide; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone