Human pancreas GH-releasing factor analog restores high-amplitude GH pulses in CNS lesion-induced GH deficiency.
Lesions of the ventromedial-arcuate (VMH-ARC) region of the hypothalamus result in impaired growth accompanied by a marked suppression in spontaneous GH secretory bursts. We studied the effects of an analog of the recently characterized human pancreas GH-releasing factor hpGRF(1-40) on GH secretory dynamics in freely-moving chronically cannulated rats bearing electrolytic lesions of the VMH-ARC. Intravenous administration of the hpGRF analog (hpGRFa) caused a dramatic surge of GH within 5 min; plasma GH levels rose to values as high as 2900 ng/ml and remained significantly elevated for 15-30 min post treatment. The simultaneous iv administration of somatostatin-14 and hpGRFa resulted in a significant inhibition of the hpGRFa-induced GH release at 5 min but not at 15 min. These results clearly demonstrate that impaired GH secretion resulting from VMH-ARC lesions can be restored by hpGRF. The findings are promising in that hpGRF and its analogs may provide valuable agents for the diagnosis and treatment of disorders of growth secondary to CNS dysfunction.
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000502:physiology*; D013006:Growth Hormone / Q000097:blood / Q000172:deficiency*; D013007:Growth Hormone-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014697:Ventromedial Hypothalamic Nucleus / Q000502:physiology*
D010446:Peptide Fragments; C038766:somatotropin releasing hormone (1-40)-OH, Ala(34)-Ser(38)-Arg(40)-; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone