Chronic central infusion of growth hormone secretagogues: Effects on Fos expression and peptide gene expression in the rat arcuate nucleus

Growth hormone (GH) secretagogues induce GH release, in part, by direct act ions upon anterior pituitary somatotropes and, in part, by actions upon the neuroendocrine circuitry that regulates GH secretion. In particular, acute systemic administration of GH secretagogues results in increased neuronal activity and Fos protein expression in the arcuate nucleus of the hypothala mus. Prolonged administration of GH secretagogues has been reported to have long-lasting effects upon GH release, promoting increased pulsatile secret ion. Here, we investigated how chronic central infusion of GH secretagogues affects the response of arcuate nucleus neurons to acute systemic administ ration of GH secretagogues. In male rats, after central infusion of GH secr etagogues for 5 days, there was no sustained expression of Fos in the arcua te nucleus, no significant induction of Fos expression in response to acute GH secretagogue challenge, and a greatly attenuated secretion of GH in res ponse to acute GH secretagogue challenge, all reflecting loss of functional responsiveness to GH secretagogues. In situ hybridisation revealed that, i n the arcuate nucleus of GH secretagogue-infused rats, mRNA levels for GH-r eleasing hormone, neuropeptide Y and somatostatin were not different than i n saline-infused animals. However, somatostatin mRNA levels in the perivent ricular nuclei of GH secretagogue-infused rats were significantly higher th an those of saline-infused rats, indicating that this nucleus may play an i mportant role in mediating the effects of chronic GH secretagogue administr ation.