Somatostatin receptors in the thymus

The thymus is the primary lymphoid organ where different factors participate in regulating the proliferation and differentiation of T cells. The thymic epithelium is the main cellular component in driving the maturation of thymocytes through cell-to-cell and extracellular matrix-mediated interactions. Thymic hormones and cytokines play a critical role in the proliferation, differentiation and selection of precursor cells along the T-cell lineage. However, other locally produced hormones and neuropeptides participate in thymic functions in an autocrine and paracrine manner. Some of them have well-characterized actions, whereas somatostatin (SS), although it has been identified, has not been investigated in detail. SS inhibits hormone and exocrine secretion, modulates neurotransmission and inhibits cell proliferation. The biological effects of SS are mediated through five G protein-coupled membrane receptor subtypes (sst(1-5)). SS receptors (SS-R) have been demonstrated in normal tissues and tumours at the protein and mRNA levels. Sst(2) mRNA has been detected in the murine thymus, whereas sst(3) and sst(4) mRNAs are expressed in the rat immune system. The significance of the presence of specific SS-R subtypes remains to be clarified. Moreover, the activation of lymphoid cells seems to modify their SS-R expression pattern. SS, sst(1), sst(2A), and sst(3) mRNAs have been found in normal human thymic tissue, whereas enriched cultured thymic epithelial cells (TEC) selectively express SS, sst(1) and sst(2A) mRNAs. Furthermore, TEC respond in vitro to SS and octreotide by inhibiting cell proliferation. Immunoreactivity for sst(2A) has been detected primarily in the medulla, where TEC, dendritic cells and macrophages are the major components, in line with the predominant binding of the sst(2) receptor-preferring ligand [I-125-Tyr(3)] -octreotide in this region. The heterogeneous distribution of SS-R subtypes on specific cell subsets indicates that SS may play a paracrine and/or autocrine role in regulating cell activities in the thymus.