ABSENCE OF GROWTH-HORMONE (GH) SECRETION AFTER THE ADMINISTRATION OF EITHER GH-RELEASING HORMONE (GHRH), GH-RELEASING PEPTIDE (GHRP-6), OR GHRH PLUS GHRP-6 IN CHILDREN WITH NEONATAL PITUITARY-STALK TRANSECTION

GH-releasing peptide (GHRP-6; His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) is a sy nthetic compound that releases GH in a specific and dose-related manne r through mechanisms and a point of action that are mostly unknown, bu t different from those of GHRH. In man, GHRP-6 is more efficacious tha n GHRH, and a striking synergistic action occurs when both compounds a re administered together. To explain such a synergistic effect, it has been postulated, but not proven, that GHRP-6 acts through a double me chanism, with actions exerted at the pituitary and the hypothalamic le vel. On the other hand, patients with the syndrome of GH deficiency du e to perinatal pituitary stalk transection have any hypothalamic facto r nonoperandi. The aim of the present study was S-fold: 1) to further understand how relevant, if at all, the hypothalamic action of GHRP-6 is for GH regulation; 2) to evaluate whether GHRP-6 plus GHRH could be a suitable diagnostic tool in children with pituitary stalk transecti on; and 3) to compare these results with similar published studies per formed in patients with hypothalamo-pituitary disconnection, who devel oped the disease as adults. Seven patients with GH deficiency and diff erent degrees of panhypopituitarism due to perinatal pituitary stalk t ransection and 7 age- and sex-matched normal controls were studied. Th e subjects underwent 3 different tests on separate occasions, being ch allenged with GHRH (1 mu g/kg, iv), GHRP-6 (1 mu/kg, iv), or GHRH plus GHRP-6. GH was analyzed as the area under the curve (mean +/- SE; mic rograms per L/90 min). In normal subjects, GH secretion was 1029 +/- 2 02 after GHRH treatment, 1221 +/- 345 after GHRP-6, and 3542 +/- 650 a fter GHRH plus GHRP-6; the latter value was significantly (P<0.05) hig her than the secretion elicited by GHRH or GHRP-6 alone. In the group of patients with perinatal pituitary stalk transection, the level of G H after GHRH treatment was 116 +/- 22 and was even more reduced (P<0.0 5) after GHRP-6 treatment (37 +/- 8). After GHRH plus GKRP-6, GH secre tion in those patients was 177 +/- 27, significantly higher (P<0.05) t han the secretion induced by either GHRH or GKRP-6 alone. Individually examined, none of the patients tested with the most potent stimulus k nown to date (GHRH plus GHRP-6) exhibited GH secretion greater than 5 mu g/L. As pointed out by GHRH action and in divergence with the situa tion observed in patients with hypothalamo-pituitary disconnection as adults, the somatotroph population is severely reduced or unresponsive to stimuli. Regarding the regulation of GH secretion, these results i ndicate that 1) the main action of GHRP-6 as well as its synergistic a ction on GHRH seem to be exerted at hypothalamic level; 2) when the pi tuitary is deprived of the hypothalamic regulation in the perinatal pe riod, a reduced number or function of somatotrophs ensues, which is no t observed when this deprivation happens in adulthood; and 3) GHRH plu s GHRP-6 may be a suitable, cheap, and side effect-free test for scree ning patients with GH deficiency.