Autoradiographic analysis of ghrelin receptors in the rat hypothalamus

Ghrelin exerts potent stimulatory effects on food intake. It is assumed to increase feeding by binding at growth hormone secretagogue receptors (GHS-R), the only sites of action for this gastric hormone identified to date. Initially, the distribution of ghrelin binding sites could only be determined from expression patterns of GHS-R mRNA or the use of immunohistochemical techniques to examine c-fos expression. However, the characterisation of a novel radioligand ([(125)I-his(9)]-ghrelin), has enabled the distribution of GHS-R receptor protein to be directly demonstrated. Here, using quantitative autoradiography, we investigate the distribution and density of ghrelin receptors in the rodent hypothalamus. Specific binding was identified in the appetite-regulating arcuate nucleus, ventromedial hypothalamic nucleus, paraventricular nucleus, dorsomedial hypothalamic nucleus and the lateral hypothalamic area corresponding to the previously reported distribution pattern of GHS-R mRNA. Surprisingly, variations in receptor density were not identified in any of these binding sites upon a change in nutritional status, despite relevant alterations in plasma ghrelin levels being identified. We suggest that this may relate to the paradigm employed to modify nutritional status in the study or could indicate that peripheral ghrelin is unlikely to be the major source of ghrelin that acts in many hypothalamic sites.