title: The smelling of Hedione results in sex-differentiated human brain activity.
abstract: A large family of vomeronasal receptors recognizes pheromone cues in many animals including most amphibia, reptiles, rhodents, and other mammals. Humans possess five vomeronasal-type 1 receptor genes (VN1R1-VN1R5), which code for proteins that are functional in recombinant expression systems. We used two different recombinant expression systems and identified Hedione as a ligand for the putative human pheromone receptor VN1R1 expressed in the human olfactory mucosa. Following the ligand identification, we employed functional magnetic resonance imaging (fMRI) in healthy volunteers to characterize the in vivo action of the VN1R1 ligand Hedione. In comparison to a common floral odor (phenylethyl alcohol), Hedione exhibited significantly enhanced activation in limbic areas (amygdala, hippocampus) and elicited a sex-differentiated response in a hypothalamic region that is associated with hormonal release. Utilizing a novel combination of methods, our results indicate that the putative human pheromone receptor VN1R1 is involved in extra-olfactory neuronal activations induced by the odorous substance Hedione. The activation of VN1R1 might play a role in gender-specific modulation of hormonal secretion in humans.
authors: Department of Cell Physiology, Ruhr University Bochum, Universitätsstr. 150, 44801 Bochum, Germany. Electronic address: ivonne.wallrabenstein@rub.de.
authors: I
authors: I
authors: Wallrabenstein
authors: Department of Neuroradiology, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany. Electronic address: johannes.gerber@uniklinikum-dresden.de.
authors: J
authors: J
authors: Gerber
authors: Department of Cell Physiology, Ruhr University Bochum, Universitätsstr. 150, 44801 Bochum, Germany. Electronic address: sebastian.rasche@rub.de.
authors: S
authors: S
authors: Rasche
authors: Department of Otorhinolaryngology, Smell and Taste Clinic, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany. Electronic address: ilona.croy@tu-dresden.de.
authors: I
authors: I
authors: Croy
authors: Department of Cell Physiology, Ruhr University Bochum, Universitätsstr. 150, 44801 Bochum, Germany. Electronic address: stefan.kurtenbach@me.com.
authors: S
authors: S
authors: Kurtenbach
authors: Department of Otorhinolaryngology, Smell and Taste Clinic, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany. Electronic address: thummel@mail.zih.tu-dresden.de.
authors: T
authors: T
authors: Hummel
authors: Department of Cell Physiology, Ruhr University Bochum, Universitätsstr. 150, 44801 Bochum, Germany. Electronic address: hanns.hatt@rub.de.
authors: H
authors: H
authors: Hatt
mesh_terms: D000328:Adult; D020013:Calcium Signaling / Q000187:drug effects; D002630:Chemotactic Factors / Q000235:genetics / Q000502:physiology; D003517:Cyclopentanes / Q000494:pharmacology*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects; D008032:Limbic System / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D008297:Male; D009831:Olfactory Mucosa / Q000187:drug effects / Q000378:metabolism; D049049:Pheromones, Human / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D043563:Receptors, Pheromone / Q000187:drug effects / Q000235:genetics; D012727:Sex Characteristics; D012903:Smell / Q000502:physiology*; D014162:Transfection; D055815:Young Adult
chemical_list: D002630:Chemotactic Factors; D003517:Cyclopentanes; D049049:Pheromones, Human; D043563:Receptors, Pheromone; C414724:VN1R1 protein, human; C501952:methyldihydrojasmonate
keywords: Hedione; Human VN1R1; Olfaction; Pheromones; Social odors; fMRI