Endocrine Abstracts

omatostatin, originally isolated from ovine hypothalami in 1973, and cortistatin, identified a decade ago in amphibians and then in human and rodents, are two highly related peptides thought to derive from a common ancestor gene. Owing to their high structural homology, both peptides bind with similar affinity to the five so-called somatostatin receptors (sst1-sst5), and exert virtually undistinguishable effects on several physiological targets, including inhibition of endocrine secretions. Yet, each peptide also shows distinctive, specific functions, which should involve different receptors and/or signalling mechanisms still to be defined, and also display divergent patterns of expression in normal and tumoral tissues. In particular, cortistatin selectively regulates locomotion- and sleep-related processes and exerts potent antiinflammatory effects with a promising therapeutic potential. In this context, recent work from our group has aimed at characterizing the response of pituitary somatotrope cells to cortistatin and somatostatin, and to isolate sst receptors in a domestic species, the pig. This led to us to demonstrate that both peptides similarly exert a dual, inhibitory and stimulatory effect on GH release in vitro, which likely involve sst1/sst2 and sst5, respectively. Furthermore, while cloning porcine sst5, we discovered two new truncated isoforms of this receptor, termed psst5B and psst5C, which display distinct tissue distribution and, when expressed in clonal cell lines, show selective functional responses to somatostatin (psst5B) and cortistatin (psst5C). Interestingly, FRET studies revealed that these novel receptors functionally interact with their full-length counterpart psst5A, as well as with the rest of pig sst. Moreover, we recently cloned two similar human sst5 truncated isoforms (hsst5B and hsst5C) that also show selective functional response to somatostatin and cortistatin, functionally interact with and modulate hsst5A and hsst2, and are differentially distributed in normal and tumoral human tissues, suggesting a possible pathophysiological role for these novel receptors.

Support: CVI-139&P06-CTS-01705-J.Andalucia, BFU2004-03883-MEC/FEDER