The role of galanin and its receptor in the feedback regulation of growth hormone secretion.

Abstract

GH controls its own secretion through a mechanism involving short-loop feedback regulation of the synthesis and release of GH-releasing hormone (GHRH). GHRH neurons coexpress the peptide galanin, but the functional significance of this coexpression is unknown. In this study, we tested the hypotheses that 1) galanin gene expression in GHRH neurons is regulated by GH and 2) somatostatin (SS) or GHRH neurons are a target for the action of galanin in the hypothalamus. First, we compared levels of galanin messenger RNA (mRNA) in GHRH neurons between normal male rats and Lewis dwarf rats, which have markedly reduced blood levels of GH. The brains of normal and dwarf animals were processed for detection of galanin mRNA and GHRH mRNA by double-label in situ hybridization. We observed that Lewis dwarf rats had significantly reduced levels of galanin mRNA in their GHRH neurons (P < 0.05). Next, we tested the 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) hypophysectomized (hypox) rats (n = 7); and 3) hypox rats treated with 1.5 mg of rat GH (rGH) over a 3-day period (n = 6). At the end of the treatment period, the animals were killed, and their brains were collected and processed for double-label in situ hybridization for GHRH mRNA and galanin mRNA. The signal level of galanin mRNA in GHRH neurons was reduced in hypox 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 differ significantly between the groups of intact and rGH-treated hypox rats. Finally, to determine whether SS or GHRH neurons are targets for galanin, we used double-label in situ hybridization to determine whether either of these populations of neurons express galanin receptor mRNA. 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 GH action, and we infer that galanin may play a role in the feedback control of GH secretion by exerting a direct effect on SS neurons.