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It is well known that somatostatin modulates thymic functions, such as binding to receptors. In order to elucidate the influence of somatostatin on the thymus architecture and the T cells maturation, young adult male rats were treated with somatostatin-28. The results showed that somatostatin-28 decreased thymus weight and cellularity, probably due to alterations in the thymic morphometric parameters. Our results also demonstrated that SRIH treatment reduces number of cells with undetectable alpha beta TCR and cells with low expression of alpha beta TCR, while the number of TCR alpha beta(hi) cells remains approximately the same as the values obtained from the control rats. Besides, in the least mature thymocytes (DNTCR TCR alpha beta(-)) and among the most mature the SPCD4 TCR alpha beta(hi) subset remained unaltered, while SPCD8 TCR alpha beta(hi) decreased. At last, it should be noted that SRIH treatment increases DN thymocytes subsets expressing TCR alpha beta(low/hi) (TCR alpha beta(+)). These results suggest that somatostatin-28 induces reshaping of T cells maturation and, at least partly, contributes to thymic weight loss, through the modulation of the complex neuroendocrine-immune network. (C) 2007 Elsevier B.V. All rights reserved.

The present study, through quantification of tyrosine hydroxylase (TH) expression and catecholamine (CA) content in the presence and in the absence of alpha-methyl-p-tyrosine (AMPT), a TH inhibitor, in adult thymic organ (ATOC) and thymocyte culture, demonstrated that thymic cells produce CAs. In addition, in ATOC an increase in beta(2)-adrenoceptor (AR) mRNA expression and beta(2)-AR thymocyte surface density was registered. Furthermore, AMPT (10(-4) M), as propranolol (10(-4) M), augmented thymocyte apoptosis and diminished thymocyte proliferation in ATOC. Propranolol exerted these effects acting on CD3(high) thymocytes. However, in thymocyte cultures, propranolol (10(-6) M) acting on the same-thymocyte subset exerted the opposing effect on thymocyte apoptosis and ConA-stimulated proliferation. This suggested that, depending on thymocyte microenvironment, differential effects can be induced through the same type of AR. Additionally, arterenol (10(-8) to 10(-6) M), similar to propranolol, diminished apoptosis, but increased ConA-stimulated thymocyte proliferation in thymocyte culture. However, differently from propranolol, arterenol affected manly CD3- thymocyte subset, which harbors majority of alpha(1)-AR+ thymocytes. Additionally, arterenol showed a dose-dependent decrease in efficiency of thymocyte apoptosis and proliferation modulation with the rise in its concentration. Considering greater affinity of arterenol for alpha(1)-ARs than for beta(2)-ARs, the previous findings could be attributable to increased engagement of beta(2)-ARs with the rise of arterenol concentration. Consistently, in the presence of propranolol (10(-6) M), a beta-AR blacker, the arterenol (10(-8) M) effects on thymocytes were augmented. In conclusion, thymic endogenous CAs, acting through distinct AR types and, possible, the same AR type (but in different cell microenvironment) may exert the opposing effects on thymocyte apoptosis/proliferation. (C) 2014 Elsevier B.V. All rights reserved.

The role of somatostatin on inhibition of both normal and tumor cell cycle, secretion of endocrine and exocrine cells, as well as induction apoptosis is well documented. However, its effect on T cell development and thymic structure is not fully clarified. In order to investigate the influence of somatostatin in vivo on the thymus structure and T cell development, the young adult Albino Oxford male rats were intracerebroventriculary treated with somatostatin-14. We examined the thymus compartments and its cellularity, through assessment of morphometric parameters by stereological method, and the relation between thymocytes subpopulations, over expression of CD4, CD8 and T-cell receptor (TCR) alpha beta by flow cytometry. Additionally, we also determined the body and thymus weight of the rats, during the first three months of life, to define the time of SRIH-14 application. A decrease of relative thymus weight from the fourth weeks of postnatal life, and an unchanged relative thymus weight obtained in treated group indicates that SRIH-14 in young adult rats inhibits growth of whole organism, not only thymus. The changes in the absolute number and numerical density of cortical thymocytes indicate that SRIH-14 alters the true lymphoid tissue. SRIH-14 changes relation between thymocyte subsets, increase number of CD4(-)CD8(-)TCR alpha beta(-) and CD4(-)CD8(+)TCR alpha beta(hi) phi thymocyte subsets as well as the CD4(-)CD8(-)TCR alpha beta(low/hi) thymocytes, while decrease number of CD4+CD8+ TCR alpha beta(low/hi) thymocyte subsets. These results indicate that somatostatin-14 is Dot involved in the control of the physiologic involution of the thymus, although induces thymic weight loss through the reduction of true lymphoid tissue. In addition, changes in frequency of thymocyte subpopulations, especially immature cells, indicate that SRIH-14 modulates thymocytes development and maturation. (C) 2007 Elsevier Ltd. All rights reserved.

Various stressors induce changes in the immune system. However, it has not yet been analyzed how stressors affect thymus innervation. To examine whether chronic stress alters the morphology of the thymus by changing the nerve components of the thymus, adult mate rats, 9-weeks old, were exposed to forced swimming during 21 successive days. The animals were sacrificed by decapitation after the last session and their thymuses were used for analysis of (i) the thymus compartments, (ii) distribution patterns of monoamine-containing nerve profiles and (iii) distribution patterns of acetylcholinesterase (AChE)-containing nerve profiles. Our results show that chronic stress in rats reduces the volume of both thymus cortex and medulla, numbers of thymocytes in the deep cortex and medulla and the density of fluorescent nerve profiles, whereas it increases density of fluorescent cells. The distribution patterns of nerve profiles containing monoamine and AChE were not affected. These changes indicate that chronic stress affects thymus development and T cell maturation by altering the sympathetic nerve component. (c) 2004 Elsevier GmbH. All rights reserved.

The aim of this study was to investigate whether chronic stress, induced by repeated daily swimming during 21 days, alters the morphofunctional parameters in the thymus of adult rats. Our results showed that chronic stress reduced thymus mass, total number of thymocytes, volume of the thymus compartments and numerical density of thymocytes within thymus inner cortex and medulla. However, the percentage of apoptotic cells and the level of corticosterone were significantly increased. The percentages of CD4-CD8-TCR alpha beta(low/high) and CD4-CD8+TCR alpha beta(-) thymocytes were significantly increased, while the percentage of the least mature CD4+CD8-SP TCR alpha beta(-) thymocytes was significantly decreased. These results show that recurred swimming procedure induces thymus hypotrophy and elevated percentage of DN TCR alpha beta(+) cells. (c) 2004 Elsevier B.V. All rights reserved.

It is well known that somatostatin exerts a wide range of effects in the body, and acts as an antocrine or paracrine factor in the thymus. However, it has not been investigated yet whether somatostatin alters the thymus size and relation among the thymocyte subpopulations in the peripubertal rats. For this purpose, the peripubertal AO male rats were cannulated intracerebroventriculary and treated with repeated, low doses of somatostatin-14 (experimental group) or saline (control group). Twenty-four hours after the last treatment, we removed and prepared the thymuses for determination of thymocyte subpopulations by flow cytometry. After five days, animals were sacrificed and their thymuses taken for morphometrical analysis by stereological methods. We noticed that somatostatin-14 decreased volumes of thymus cortex and medulla, total number of thymocytes, number of thymocytes in the cortex and medulla and numerical density of thymocytes in deeper cortex. As a consequence of these changes, thymus size was also diminished. The phenotypic analysis of thymocyte subpopulations showed that somatostatin-14 decreased the percentage of CD4(+)CD8(+) cells with low level of TCRalphabeta expression, positively selected CD4(+)CD8(+)TCRalphabeta(high) cells and the most mature CD4(-)CD8(+)TCRalphabeta(high) cells, while the percentage of CD4(+)CD8(-)TCRalphabeta(high) thymocytes was slightly increased. Somatostatin-14 increased the relative proportion of the least mature CD4(-)CD8(-)TCRalphabeta(-/low), CD4(+)CD8(+)TCRalphabeta(-) cells and both of TCRalphabeta(-/low) single positive subpopulations. These results show that centrally applied somatostatin-14, induces hypotrophy of the thymus in peripubertal rats by changing the volumes and cellularities of the thymic compartments. Additionally, increased number of the least mature thymocytes and a deficiency of double positive cells indicate the involvement of somatostatin in the modulation of T cells maturation. (C) 2003 Elsevier Ltd. All rights reserved.

The aim of this study was to investigate the effects of centrally applied somatostatin-28 on morphometric characteristics of the thymus, the thymocyte subpopulations, as well as, on apoptosis and phases of cell cycle in thymocytes. For this purpose, peripubertal male rats were cannulated intracerebroventriculary and treated with repeated, nanomolar concentrations of somatostatin-28 (experimental group) or saline (control group). Animals were sacrificed and their thymuses were used for the analysis of thymocyte subpopulations, cell cycle and apoptosis by flow cytometry and for the evaluation of morphometric parameters by stereological analysis. Our results showed that somatostatin-28 caused decrease of the thymic mass and volume, as well as total thymocytes number. Stereological analysis revealed volume decrease of thymic cortex and medulla accompanied with cellularity decrease. Somatostatin in the deeper cortex decreased the number of thymocytes, per volume unit, while in outer cortex raised their number. A significant increase in the percentage of double-negative and both single-positive thymocyte subpopulations, in parallel with a diminished percentage of double-positive cells was found. The cellularity of double-positive and single-positive thymocyte subpopulations was decreased. Somatostatin-28 treatment augmented the percentage of apoptotic cells, while the percentage of the cells represented in phases of cell cycle was reduced. These results suggest that somatostatin-28 induce thymus hypotrophy as result of decreasing cortex and medulla volume and cellularity. Changes in the percentage and cellularity of thymocyte subpopulations and numerical density of thymocytes in outer and deeper cortex, indicate that somatostatin-28 evoked disturbance in transition of double-negative to double-positive thymocytes.