PMID- 29483934 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240313 IS - 1742-9994 (Print) IS - 1742-9994 (Electronic) IS - 1742-9994 (Linking) VI - 15 DP - 2018 TI - Two predominant MUPs, OBP3 and MUP13, are male pheromones in rats. PG - 6 LID - 10.1186/s12983-018-0254-0 [doi] LID - 6 AB - BACKGROUND: In rats, urine-borne male pheromones comprise organic volatile compounds and major urinary proteins (MUPs). A number of volatile pheromones have been reported, but no MUP pheromones have been identified in rat urine. RESULTS: We used sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), isoelectric focusing electrophoresis (IEF), nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS) after in gel digestion of the proteins and quantitative real-time PCR (qRT-PCR) and showed that the levels of two MUPs, odorant-binding protein 3 (OBP3) (i.e. PGCL4) and MUP13 (i.e. PGCL1), in urine and their mRNAs in liver were higher in males than in females and were suppressed by orchidectomy and restored by testosterone treatment (T treatment). We then generated recombinant MUPs (rMUPs) and found that the sexual attractiveness of urine from castrated males to females significantly increased after the addition of either recombinant OBP3 (rOBP3) or recombinant MUP13 (rMUP13). Using c-Fos immunohistochemistry, we further examined neuronal activation in the brains of female rats after they sniffed rOBP3 or rMUP13. Both rOBP3 and rMUP13 activated the accessory olfactory bulb (AOB), medial preoptic area (MPA), bed nucleus of the stria terminalis (BST), medial amygdala (MeA), posteromedial cortical amygdala (PMCo) and ventromedial nucleus of the hypothalamus (VMH), which participate in the neural circuits responsible for pheromone-induced sexual behaviours. In particular, more c-Fos-immunopositive (c-Fos-ir) cells were observed in the posterior AOB than in the anterior AOB. CONCLUSIONS: The expression of OBP3 and MUP13 was male-biased and androgen-dependent. They attracted females and activated brain areas related to sexual behaviours in female rats, suggesting that both OBP3 and MUP13 are male pheromones in rats. Particularly, an OBP excreted into urine was exemplified to be a chemical signal. FAU - Guo, Xiao AU - Guo X AD - 1State Key Laboratory of Integrated Management of Pest Insects and Rodents in Agriculture, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichen West Road, Beijing, 100101 China. ISNI: 0000 0004 1792 6416. GRID: grid.458458.0 AD - 2University of Chinese Academy of Sciences, Beijing, 100049 China. ISNI: 0000 0004 1797 8419. GRID: grid.410726.6 FAU - Guo, Huifen AU - Guo H AD - 1State Key Laboratory of Integrated Management of Pest Insects and Rodents in Agriculture, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichen West Road, Beijing, 100101 China. ISNI: 0000 0004 1792 6416. GRID: grid.458458.0 FAU - Zhao, Lei AU - Zhao L AD - 1State Key Laboratory of Integrated Management of Pest Insects and Rodents in Agriculture, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichen West Road, Beijing, 100101 China. ISNI: 0000 0004 1792 6416. GRID: grid.458458.0 AD - 2University of Chinese Academy of Sciences, Beijing, 100049 China. ISNI: 0000 0004 1797 8419. GRID: grid.410726.6 FAU - Zhang, Yao-Hua AU - Zhang YH AUID- ORCID: 0000-0002-6318-413X AD - 1State Key Laboratory of Integrated Management of Pest Insects and Rodents in Agriculture, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichen West Road, Beijing, 100101 China. ISNI: 0000 0004 1792 6416. GRID: grid.458458.0 FAU - Zhang, Jian-Xu AU - Zhang JX AD - 1State Key Laboratory of Integrated Management of Pest Insects and Rodents in Agriculture, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichen West Road, Beijing, 100101 China. ISNI: 0000 0004 1792 6416. GRID: grid.458458.0 LA - eng PT - Journal Article DEP - 20180223 PL - England TA - Front Zool JT - Frontiers in zoology JID - 101231669 PMC - PMC5824612 OTO - NOTNLM OT - Activation of neural pathways OT - Female attraction OT - MUPs OT - Male pheromones COIS- The procedures for animal care and use were performed in strict accordance with the guidelines of the Animal Use Committee of the Institute of Zoology, Chinese Academy of Sciences (IOZ 2015).Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/02/28 06:00 MHDA- 2018/02/28 06:01 PMCR- 2018/02/23 CRDT- 2018/02/28 06:00 PHST- 2017/08/08 00:00 [received] PHST- 2018/02/02 00:00 [accepted] PHST- 2018/02/28 06:00 [entrez] PHST- 2018/02/28 06:00 [pubmed] PHST- 2018/02/28 06:01 [medline] PHST- 2018/02/23 00:00 [pmc-release] AID - 254 [pii] AID - 10.1186/s12983-018-0254-0 [doi] PST - epublish SO - Front Zool. 2018 Feb 23;15:6. doi: 10.1186/s12983-018-0254-0. eCollection 2018.