Developmental expression and serotonergic regulation of relaxin 3/INSL7 in the nucleus incertus of rat brain

Relaxin 3 or insulin like peptide 7 has been identified as a new member of the insulin/relaxin superfamily. We recently reported that relaxin 3 was dominantly expressed in the brain, particularly in neurons of the nucleus incertus (NI) of the median dorsal tegmental pons and that it might act as a neurotransmitter. In the present study we investigated the developmental expression and serotonergic regulation of relaxin 3 gene in the rat brain. Relaxin 3 mRNA appeared at embryonic day 18 in the near region of the fourth ventricle, and was shown to have increased its density and the number of expressing neurons by in situ hybridization and RT-PCR examination. Relaxin 3 peptide was detected after birth by immunocytochemistry. Since the NI is located just caudal to the dorsal raphe nucleus where abundant serotonin (5-HT) neurons are present, we examined if 5-HT effects on the expression of relaxin 3. Relaxin 3 gene expression in the NI significantly increased after 5-HT depletion by p-chlorophenylalanine (PCPA) administration. We also observed the 5-HT1A receptor localization in relaxin 3 positive neurons of the NI. This result suggests that 5-HT negatively regulates the expression of relaxin 3 gene in the NI. The function of relaxin 3 neurons in the brain is influenced by the serotonergic activity.