Abstract
The peptide hormone ghrelin binds to the GH secretagogue receptor (GHS-R), stimulates GH secretion, and promotes adipogenesis. However, continuous GHS infusion does not stimulate skeletal growth and is associated with desensitization to further GH secretagogue treatment. In this study, 7-d intermittent (i.e. every 3 h) infusion of ghrelin, or the GH secretagogue, GH-releasing peptide-6, in the moderately GH- deficient transgenic growth-retarded rat, augmented GH secretion, leading to a sustained acceleration in skeletal growth. In contrast, continuous infusion of ghrelin, or GH-releasing peptide-6, suppressed the amplitude of spontaneous GH secretory episodes and produced only a transient increase in body weight gain. The reduction in GH secretion seen with continuous GHS-R activation was not associated with a desensitization of the pituitary to GH-releasing factor or to down-regulation of hypothalamic GHS-R mRNA expression. Continuous ghrelin treatment elicited an increase in somatostatin mRNA expression in the periventricular nuclei. Thus, exposure to continuously elevated circulating ghrelin may be responsible for the suppression of GH secretion reported in rats after prolonged starvation.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Animals, Genetically Modified
-
Aryl Hydrocarbon Hydroxylases / metabolism
-
Body Weight / drug effects
-
Cytochrome P450 Family 2
-
Drug Administration Schedule
-
Drug Synergism
-
Dwarfism, Pituitary / genetics
-
Dwarfism, Pituitary / pathology
-
Dwarfism, Pituitary / physiopathology*
-
Gene Expression / drug effects
-
Ghrelin
-
Growth / drug effects
-
Growth Hormone / antagonists & inhibitors*
-
Growth Hormone / deficiency*
-
Growth Hormone / metabolism
-
Growth Hormone-Releasing Hormone / pharmacology
-
Hypothalamus / physiopathology
-
Infusions, Intravenous
-
Liver / metabolism
-
Male
-
Oligopeptides / administration & dosage*
-
Peptide Hormones / administration & dosage*
-
Pulsatile Flow
-
Rats
-
Receptors, G-Protein-Coupled / metabolism
-
Receptors, Ghrelin
-
Steroid 16-alpha-Hydroxylase / metabolism
-
Steroid Hydroxylases / metabolism
Substances
-
Ghrelin
-
Oligopeptides
-
Peptide Hormones
-
Receptors, G-Protein-Coupled
-
Receptors, Ghrelin
-
growth hormone releasing hexapeptide
-
Growth Hormone
-
Growth Hormone-Releasing Hormone
-
Steroid Hydroxylases
-
Aryl Hydrocarbon Hydroxylases
-
CYP2C11 protein, rat
-
Cytochrome P450 Family 2
-
Steroid 16-alpha-Hydroxylase
-
steroid 15-beta-hydroxylase