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 horm one (GH) from the anterior pituitary gland and in regulating the activity o f hypothalamic growth hormone-releasing hormone (GHRH) neurones. GH secreta gogues act at both the pituitary and the hypothalamus to facilitate the rel ease of GH. In male rats, using the induction of Fos protein as an indicato r of neuronal activation, we examined whether neurones in the brainstem, th e 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 se cretagogue-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 neu rotoxin, 5-ADMP, did not alter GH secretagogue-induced activation of Fos pr otein in the arcuate nucleus compared to vehicle-treated controls. We concl ude that the central actions of GH secretagogues involve the activation of non-noradrenergic cells in the area postrema and that GH secretagogue-induc ed activation of the arcuate nucleus occurs independently of noradrenergic tone.