Growth hormone secretagogue activation of the arcuate nucleus and brainstem occurs via a non-noradrenergic pathway.
Noradrenergic systems are integrally involved in the release of growth hormone (GH) from the anterior pituitary gland and in regulating the activity of hypothalamic growth hormone-releasing hormone (GHRH) neurones. GH secretagogues act at both the pituitary and the hypothalamus to facilitate the release of GH. In male rats, using the induction of Fos protein as an indicator of neuronal activation, we examined whether neurones in the brainstem, the main noradrenergic input to the hypothalamus, were activated by systemic administration of peptide and non-peptide GH secretagogues. In addition, we examined the effects of chronic central noradrenaline depletion upon GH secretagogue-induced activation of the arcuate nucleus. Systemic injection of the GH secretagogues, GHRP-6 and MK-0677 induced Fos protein expression in a population of area postrema cells, but less than 10% of these cells were noradrenergic. Depletion of hypothalamic noradrenaline by the specific neurotoxin, 5-ADMP, did not alter GH secretagogue-induced activation of Fos protein in the arcuate nucleus compared to vehicle-treated controls. We conclude that the central actions of GH secretagogues involve the activation of non-noradrenergic cells in the area postrema and that GH secretagogue-induced activation of the arcuate nucleus occurs independently of noradrenergic tone.
Bailey
A R
AR
Department of Biomedical Sciences, University Medical School, George Square, Edinburgh, UK. abailey@bcm.tmc.edu
von Engelhardt
N
N
Von Englehardt
N
N
Leng
G
G
Smith
R G
RG
Dickson
S L
SL
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D001933:Brain Stem / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009498:Neurotoxins / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D010627:Phenethylamines / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013141:Spiro Compounds / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D007211:Indoles; D009498:Neurotoxins; D009842:Oligopeptides; D010627:Phenethylamines; D016760:Proto-Oncogene Proteins c-fos; D013141:Spiro Compounds; C072819:5-amino-2,4-dihydroxy-alpha-methylphenylethylamine; C041048:growth hormone releasing hexapeptide; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D014446:Tyrosine 3-Monooxygenase; C094817:ibutamoren mesylate