Endocrine Modulation of Olfactory Responsiveness: Effects of the Orexigenic Hormone Ghrelin.

Finding food sources is a prerequisite for an acute food intake. This process is initiated by ghrelin released from X/A-like cells of the gastrointestinal tract. Because food finding often depends on olfaction, the question arises whether ghrelin may affect the responsiveness of the olfactory system. Monitoring odor-induced activation of the mouse olfactory epithelium via Egr1 expression revealed that after a nasal application of ghrelin, more sensory neurons responded upon odor exposure indicating an increased responsiveness. The higher reactivity of olfactory neurons was accompanied with an increased activity of receptor-specific glomeruli. In search for mechanisms underlying the ghrelin-mediated sensitization of olfactory neurons, it was shown that Ghsr1a, the ghrelin receptor gene, but not the hormone itself was expressed in the olfactory epithelium. Further analysis of isolated cells revealed that the receptor was in fact expressed in mature olfactory sensory neurons. Treatment with a ghrelin receptor antagonist abolished the ghrelin effect, strengthening the notion that ghrelin and its receptor are responsible for the enhanced neuronal responsiveness. In contrast to the effects of the "hunger" hormone ghrelin, the short-term "satiety" hormone PYY3-36 did not affect olfactory responsiveness. The results demonstrate that ghrelin, which signals acute hunger, renders the olfactory system more responsive to odors.

Adiponectin enhances the responsiveness of the olfactory system.

The peptide hormone adiponectin is secreted by adipose tissue and the circulating concentration is reversely correlated with body fat mass; it is considered as starvation signal. The observation that mature sensory neurons of the main olfactory epithelium express the adiponectin receptor 1 has led to the concept that adiponectin may affect the responsiveness of the olfactory system. In fact, electroolfactogram recordings from olfactory epithelium incubated with exogenous adiponectin resulted in large amplitudes upon odor stimulation. To determine whether the responsiveness of the olfactory sensory neurons was enhanced, we have monitored the odorant-induced expression of the immediate early gene Egr1. It was found that in an olfactory epithelium incubated with nasally applied adiponectin the number of Egr1 positive cells was significantly higher compared to controls, suggesting that adiponectin rendered the olfactory neurons more responsive to an odorant stimulus. To analyze whether the augmented responsiveness of sensory neurons was strong enough to elicit a higher neuronal activity in the olfactory bulb, the number of activated periglomerular cells of a distinct glomerulus was determined by monitoring the stimulus-induced expression of c-fos. The studies were performed using the transgenic mOR256-17-IRES-tauGFP mice which allowed to visualize the corresponding glomerulus and to stimulate with a known ligand. The data indicate that upon exposure to 2,3-hexanedione in adiponectin-treated mice the number of activated periglomerular neurons was significantly increased compared to controls. The results of this study indicate that adiponectin increases the responsiveness of the olfactory system, probably due to a higher responsiveness of olfactory sensory neurons.