TY - JOUR
T1 - Sulfated steroids as natural ligands of mouse pheromone-sensing neurons
AU - Nodari, Francesco
AU - Hsu, Fong Fu
AU - Fu, Xiaoyan
AU - Holekamp, Terrence F.
AU - Kao, Lung Fa
AU - Turk, John
AU - Holy, Timothy E.
PY - 2008/6/18
Y1 - 2008/6/18
N2 - Among mice, pheromones and other social odor cues convey information about sex, social status, and identity; however, the molecular nature of these cues is essentially unknown. To identify these cues, we screened chromatographic fractions of female mouse urine for their ability to cause reproducible firing rate increases in the pheromone-detecting vomeronasal sensory neurons (VSNs) using multielectrode array (MEA) recording. Active compounds were found to be remarkably homogenous in their basic properties, with most being of low molecular weight, moderate hydrophobicity, low volatility, and possessing a negative electric charge. Purification and structural analysis of active compounds revealed multiple sulfated steroids, of which two were identified as sulfated glucocorticoids, including corticosterone 21-sulfate. Sulfatase-treated urine extracts lost >80%of their activity, indicating that sulfated compounds are the predominant VSN ligands in female mouse urine. As measured by MEA recording, a collection of 31 synthetic sulfated steroids triggered responses 30-fold more frequently than did a similarly sized stimulus set containing the majority of all previously reported VSN ligands. Collectively, VSNs detected all major classes of sulfated steroids, but individual neurons were sensitive to small variations in chemical structure. VSNs from both males and females detected sulfated steroids, but knock-outs for the sensory transduction channel TRPC2 did not detect these compounds. Urine concentrations of the two sulfated glucocorticoids increased many fold in stressed animals, indicating that information about physiological status is encoded by the urine concentration of particular sulfated steroids. These results provide an unprecedented characterization of the signals available for chemical communication among mice.
AB - Among mice, pheromones and other social odor cues convey information about sex, social status, and identity; however, the molecular nature of these cues is essentially unknown. To identify these cues, we screened chromatographic fractions of female mouse urine for their ability to cause reproducible firing rate increases in the pheromone-detecting vomeronasal sensory neurons (VSNs) using multielectrode array (MEA) recording. Active compounds were found to be remarkably homogenous in their basic properties, with most being of low molecular weight, moderate hydrophobicity, low volatility, and possessing a negative electric charge. Purification and structural analysis of active compounds revealed multiple sulfated steroids, of which two were identified as sulfated glucocorticoids, including corticosterone 21-sulfate. Sulfatase-treated urine extracts lost >80%of their activity, indicating that sulfated compounds are the predominant VSN ligands in female mouse urine. As measured by MEA recording, a collection of 31 synthetic sulfated steroids triggered responses 30-fold more frequently than did a similarly sized stimulus set containing the majority of all previously reported VSN ligands. Collectively, VSNs detected all major classes of sulfated steroids, but individual neurons were sensitive to small variations in chemical structure. VSNs from both males and females detected sulfated steroids, but knock-outs for the sensory transduction channel TRPC2 did not detect these compounds. Urine concentrations of the two sulfated glucocorticoids increased many fold in stressed animals, indicating that information about physiological status is encoded by the urine concentration of particular sulfated steroids. These results provide an unprecedented characterization of the signals available for chemical communication among mice.
KW - Glucocorticoids
KW - Multielectrode array
KW - Olfactory
KW - Stress
KW - Tuning
KW - Vomeronasal
UR - http://www.scopus.com/inward/record.url?scp=46749147573&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.1425-08.2008
DO - 10.1523/JNEUROSCI.1425-08.2008
M3 - Article
C2 - 18562612
AN - SCOPUS:46749147573
VL - 28
SP - 6407
EP - 6418
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 25
ER -