SYSTEMIC ADMINISTRATION OF GROWTH HORMONE-RELEASING PEPTIDE ACTIVATES HYPOTHALAMIC ARCUATE NEURONS

The synthetic hexapeptide growth hormone-releasing peptide selectively releases growth hormone in many species including man.3 Growth hormone-releasing peptide directly stimulates growth hormone release by an action at the level of the pituitary,2 at a different receptor site to that for the endogenous 44-amino acid peptide, growth hormone-releasing hormone,1 and when administered with growth hormone-releasing hormone has a synergistic effect .4 In addition to this pituitary action, we have suggested that the potent in vivo growth hormone-releasing activity of growth hormone-releasing peptide reflects a hypothalamic action 6 and growth hormone-releasing peptide binding sites have been reported to be present in the hypothalamus.7 We have now found more direct evidence for a hypothalamic action of growth hormone-releasing peptide in two ways. First, we have found that a sub-population of hypothalamic neurons show strongly increased fos expression in response to systemic growth hormone-releasing peptide administration. Fos is the protein product of the immediate early gene, c-fos, which is induced in many neuronal systems following their activation.9,12 Second, extracellular recordings from putative growth hormone-releasing hormone neurons in the arcuate nucleus showed that growth hormone-releasing peptide also stimulates the firing of neurons in this area.