THE ROLE OF GALANIN AND ITS RECEPTOR IN THE FEEDBACK-REGULATION OF GROWTH-HORMONE SECRETION

GH controls its own secretion through a mechanism involving short-loop feedback regulation of the synthesis and release of GH-releasing horm one (GHRH). GHRH neurons coexpress the peptide galanin, but the functi onal significance of this coexpression is unknown. In this study, we t ested the hypotheses that 1) galanin gene expression in GHRH neurons i s regulated by GH and 2) somatostatin (SS) or GHRH neurons are a targe t for the action of galanin in the hypothalamus. First, we compared le vels of galanin messenger RNA (mRNA) in GHRH neurons between normal ma le rats and Lewis dwarf rats, which have markedly reduced blood levels of GH. The brains of normal and dwarf animals were processed for dete ction of galanin mRNA and GHRH mRNA by double-label in situ hybridizat ion. We observed that Lewis dwarf rats had significantly reduced level s of galanin mRNA in their GHRH neurons (P < 0.05). Next, we tested th e hypothesis that GH regulates galanin gene expression in GHRH neurons by experimentally altering circulating levels of GH. Three groups of adult male rats were used: 1) intact rats (n = 7); 2) hypophysectomize d (hyper) rats (n = 7); and 3) hyper rats treated with 1.5 mg of rat G H (rGH) over a 3-day period (n = 6). At the end of the treatment perio d, the animals were killed, and their brains were collected and proces sed for double-label in situ hybridization for GHRH mRNA and galanin m RNA. The signal level of galanin mRNA in GHRH neurons was reduced in h yper animals to less than 10% of that in intact controls (P < 0.0001); whereas, the levels of galanin mRNA signal in GHRH neurons did not di ffer significantly between the groups of intact and rGH-treated hyper rats. Finally, to determine whether SS or GHRH neurons are targets for galanin, we used double-label in situ hybridization to determine whet her either of these populations of neurons express galanin receptor mR NA. A subset of SS neurons in the PeN appeared to express the galanin receptor mRNA, whereas few, if any, GHRH neurons appeared to do so. We conclude that galanin, like its cotransmitter GHRH, is a target for G H action, and we infer that galanin may play a role in the feedback co ntrol of GH secretion by exerting a direct effect on SS neurons.