Somatostatin receptors in the thymus

The thymus is the primary lymphoid organ where different factors participat e in regulating the proliferation and differentiation of T cells. The thymi c epithelium is the main cellular component in driving the maturation of th ymocytes through cell-to-cell and extracellular matrix-mediated interaction s. 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 we ll-characterized actions, whereas somatostatin (SS), although it has been i dentified, has not been investigated in detail. SS inhibits hormone and exo crine secretion, modulates neurotransmission and inhibits cell proliferatio n. The biological effects of SS are mediated through five G protein-coupled membrane receptor subtypes (sst(1-5)). SS receptors (SS-R) have been demon strated 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) mR NAs are expressed in the rat immune system. The significance of the presenc e of specific SS-R subtypes remains to be clarified. Moreover, the activati on 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 tissu e, whereas enriched cultured thymic epithelial cells (TEC) selectively expr ess SS, sst(1) and sst(2A) mRNAs. Furthermore, TEC respond in vitro to SS a nd octreotide by inhibiting cell proliferation. Immunoreactivity for sst(2A ) has been detected primarily in the medulla, where TEC, dendritic cells an d macrophages are the major components, in line with the predominant bindin g of the sst(2) receptor-preferring ligand [I-125-Tyr(3)] -octreotide in th is region. The heterogeneous distribution of SS-R subtypes on specific cell subsets indicates that SS may play a paracrine and/or autocrine role in re gulating cell activities in the thymus.