title: Structural characterization of sulfated steroids that activate mouse pheromone-sensing neurons.
abstract: In many species, social behavior is organized via chemical signaling. While many of these signals have been identified for insects, the chemical identity of these social cues (often called pheromones) for mammals is largely unknown. We recently isolated these chemical cues that caused firing in the pheromone-sensing neurons of the vomeronasal organ from female mouse urine [Nodari, F., et al. (2008) J. Neurosci. 28, 6407-6418]. Here, we report their structural characterization. Mass spectrometric approaches, including tandem quadrupole, multiple-stage linear ion trap, high-resolution mass spectrometry, and H-D exchange followed by ESI mass spectrometry, along with (1)H and (13)C nuclear magnetic resonance spectroscopy, including two-dimensional correlation spectroscopy, total correlation spectroscopy, heteronuclear multiple-quantum coherence, and NOE, were used to identify two sulfated steroids, 4-pregnene-11beta,20,21-triol-3-one 21-sulfate (I) (the configuration at C20 was not deduced) and 4-pregnene-11beta,21-diol-3,20-dione 21-sulfate (II), whose presence is sex-specific. The identification of this novel class of mammalian social signaling compounds suggests that steroid hormones, upon conjugation, assume a new biological role, conveying information about the organism's identity and physiological state.
authors.affiliation: Department of Internal Medicine, Mass Spectrometry Resource, Division of Endocrinology, Diabetes, Metabolism, Washington University School of Medicine, St. Louis, Missouri 63110, USA. fhsu@im.wustl.edu
authors.forename: Fong-Fu
authors.initials: FF
authors.lastname: Hsu
authors.forename: Francesco
authors.initials: F
authors.lastname: Nodari
authors.forename: Lung-Fa
authors.initials: LF
authors.lastname: Kao
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Fu
authors.forename: Terrence F
authors.initials: TF
authors.lastname: Holekamp
authors.forename: John
authors.initials: J
authors.lastname: Turk
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Holy
mesh_terms: D000818:Animals; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D015394:Molecular Structure; D009474:Neurons; D010675:Pheromones; D011282:Pregnenediones / Q000737:chemistry*; D013256:Steroids / Q000737:chemistry*; D013431:Sulfates / Q000737:chemistry*
chemical_list: D010675:Pheromones; D011282:Pregnenediones; D013256:Steroids; D013431:Sulfates