| Title: | Sulfated steroids as natural ligands of mouse pheromone-sensing neurons |
| Author(s): | Nodari F; Hsu FF; Fu X; Holekamp TF; Kao LF; Turk J; Holy TE; |
| Address: | "Department of Anatomy and Neurobiology, School of Medicine, Washington University in St. Louis, St. Louis, Missouri 63110, USA" |
| DOI: | 10.1523/JNEUROSCI.1425-08.2008 |
| ISSN/ISBN: | 1529-2401 (Electronic) 0270-6474 (Print) 0270-6474 (Linking) |
| Abstract: | "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" |
| Keywords: | "Animals;Animals Female Ligands Male Mice Mice, Inbred BALB C Neurons/*metabolism Pheromones/*metabolism/urine Steroids/*metabolism/urine Sulfates/*metabolism/urine Vomeronasal Organ/metabolism;" |
| Notes: | "MedlineNodari, Francesco Hsu, Fong-Fu Fu, Xiaoyan Holekamp, Terrence F Kao, Lung-Fa Turk, John Holy, Timothy E eng R37 DK034388/DK/NIDDK NIH HHS/ P30 DK056341-069003/DK/NIDDK NIH HHS/ R37 DK034388-25/DK/NIDDK NIH HHS/ P60 DK020579/DK/NIDDK NIH HHS/ P60 DK020579-298817/DK/NIDDK NIH HHS/ R01-DC005964/DC/NIDCD NIH HHS/ P60-DK20579/DK/NIDDK NIH HHS/ R01 DC005964-05/DC/NIDCD NIH HHS/ P30 DK056341-08/DK/NIDDK NIH HHS/ P30 DK056341/DK/NIDDK NIH HHS/ P30 DK056341-07/DK/NIDDK NIH HHS/ R37-DK34388/DK/NIDDK NIH HHS/ P41 RR000954-317581/RR/NCRR NIH HHS/ R01 DC005964/DC/NIDCD NIH HHS/ P41 RR000954/RR/NCRR NIH HHS/ P41-RR00954/RR/NCRR NIH HHS/ P30-DK56341/DK/NIDDK NIH HHS/ Comparative Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2008/06/20 J Neurosci. 2008 Jun 18; 28(25):6407-18. doi: 10.1523/JNEUROSCI.1425-08.2008" |
