SULFATED STEROIDS AS NATURAL LIGANDS OF MOUSE PHEROMONE-SENSING NEURONS

硫酸类固醇作为小鼠信息素感知神经元的天然配体

• 批准号: 8168833
• 负责人: Timothy Holy
• 金额: $ 0.64万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-10 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168833
• 关键词: Afferent Neurons; Animals; Charge; Chemical Structure; Chemicals; Collection; Communication; Computer Retrieval of Information on Scientific Projects Database; Corticosterone; Cues; Female; Funding; Glucocorticoids; Grant; Hydrophobicity; Individual; Inorganic Sulfates; Institution; Ligands; Measures; Molecular; Molecular Weight; Mus; Nature; Neurons; Odors; Pheromone; Physiological; Property; Reporting; Research; Research Personnel; Resources; Sensory; Signal Transduction; Social status; Source; Stimulus; Stress; Sulfatases; United States National Institutes of Health; Unspecified or Sulfate Ion Sulfates; Urine; Variant; male; response; sex; social; steroid sulfate

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

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