Neuroanatomic Basis of Ghrelin Action

Over the last several years, great strides have been made in elucidating the hormones and central pathways involved in regulating feeding behavior and energy balance. Ghrelin, the stomach-derived endogenous ligand for the growth hormone secretagogue receptor (GHSR; ghrelin receptor) is now established as one of the key hormonal signals of energy insufficiency. Although the central nervous system circuitry activated by systemic ghrelin has been investigated, including the important role played by the hypothalamic arcuate nucleus, the role of ghrelin-responsive neurons outside of the hypothalamus and the chemical phenotype of these ghrelin-responsive neurons remain largely uncharacterized. We have been using neuroanatomical approaches, including in situ hybridization histochemistry (ISHH), to examine more closely the central expression patterns of the ghrelin receptor, paying special attention to its expression in the brainstem. In addition, we have been using combinations of ISHH and immunohistochemistry to further characterize the chemical phenotypes of subsets of these GHSR-expressing neurons. Our preliminary findings suggest that in addition to the hypothalamic targets described previously, ghrelin may also target key brainstem cell groups involved in regulating autonomic and behavioral responses to changes in metabolic status.