Italian Society of Endocrinology Career Award Lecture: from somatostatin to…somatomedin.

Somatostatin plays different parts in hormonal regulation through 5 specific receptors in human body. It has two interesting actions such as an antisecretory activity, mostly on the gastrointestinal system and pituitary level, and an antiproliferative action on tumor cells. Many synthetic somatostatin analogues, more stable than the natural one, have been developed and two are already used in different clinical settings, including endocrine oncology. The inhibitory action on tumor growth may result from both indirect actions, namely the suppression of growth factors and growth-promoting hormones (e.g., GH/IGF-I axis) and inhibition of angiogenesis, as well as modulation of the immune system, and direct actions, such as activation of anti-growth activities (e.g., apoptosis). Recently, the development of specific polyclonal antibodies allowed the precise identification of the 5 specific somatostatin receptors and their localization in different cell species. Somatostatin receptor subtypes belong to the G protein-coupled receptor family, share a common molecular topology, and can traffic not only in vitro within different cell types but also in vivo. A picture of the pathways and proteins involved in these processes is beginning to emerge. Moreover, the process of homo- and/or heterodimerization of G-protein coupled receptors and receptor tyrosine kinase families are crucial for implicating the fundamental properties of receptor proteins including receptor expression, trafficking, and desensitization, as well as signal transduction. Furthermore, functional consequences of such an interaction in modulation of signaling pathways linked to pathological conditions specifically in cancer are discussed.