The neuropeptide somatostatin (SRIF) exerts a wide variety of actions through five SRIF receptors (sst1-5). However, not all SRIF actions can be explained by activation of the known sst. In this context, our research group has identified two novel isoforms of sst subtype 5 (sst5A) named sst5B and sst5C expressed in human and pig. These isoforms are generated by splicing of cryptic introns within the coding sequence, which alters the open reading frame, and results in new, truncated receptors with different size and sequence as compared to sst5A. Given that rodents are widely used to study the physiological importance of gene products because of the ability to generate genetically modified mice over- or under-expressing the product of interest, the current study was focused on the identification of new murine sst5 isoforms. Use of molecular biology techniques to search for partial sequences of truncated sst5 isoforms in rodents led to the identification of one sequence in rat, and two in mouse, one of which showed high interspecific nucleotide and amino acid sequence identity. Conversely, these truncated murine sst5 were not homologues to the human and porcine sst5 isoforms identified originally. Undergoing studies indicate that these sst5 isoforms display differential tissue expression patterns. Use of mice models under different physiological conditions (i.e. fasting, obesity, SRIF-knockout) has revealed that these isoforms are also differentially regulated in both pituitary and hypothalamus. Taken together, the differential pattern of expression and regulation of the sst5 isoforms, coupled to the fact that these isoforms are highly conserved in rodents suggests that these new truncated receptors may be of physiological relevance. Future experiments will focus on the study of the potential involvement of these new sst isoforms in mediating the unique SRIF actions that can not be explained with the known sst identified to date.
Support: CVI-139 and CTS-1705-J Andalucia; BFU2004-03883 and BFU2007-60180-MEC/FEDER-Spain.
03 - 07 May 2008
European Society of Endocrinology