Analysis of a novel peptide INSL7 in the central nervous system

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We have investigated physiological function of a newly identified peptide 3 years ago called, insulin like peptide 7 (INSL7) or relaxin3 which belongs to the insulin super family.1.First year, we revealed the distribution of INSL7 expression in the central nervous system using rats. It was dominantly expressed in the restricted area in the brainstem, called nucleus incertus (NI) which was located in the pontine gray matter near the fourth ventricle. It was exclusively expressed in the neurons but not glial cells and INSL7 positive neurons project axons to the forebrain ascendingly. Dense INSL7 fibers were observed in the limbic system such as septal nucleus, hippocampus and hypothtalamus. Ultrastructural examination revealed that INSL7 was diffusely distributed in the neueronal perikarya. In the axon terminals, it was included in the dense-cored vesicles near the synapse. INSL7 was strongly suggested that it is excreted into the synaptic space like a peptide neurotransmitter.2.Second year, we pursued the functional aspect of this peptide. We obtained the coexpression of INSL7 and CRF type 1 receptor. As CRF is well known as a stress-responded peptide in the brain, we examined the c-Fos expression after CRF injection in the lateral ventricle and restrained stress. Both experiments showed the immediate induction of c-Fos protein INSL7 neurons in the NI after CRF injection or restrained stress. Moreover, we confirmed INSL7 mRNA expression in the NI was increased after the restrained stress. These results indicate that INSL7 is involved in the regulation of stress response in the brain. We published the data mentioned above in the reference 1 and 2. Other references were also published using similar histochemical techniques.