CROSS-TALK BETWEEN ENDOCRINE SYSTEM AND OTHER BIOLOGICAL PATHWAYS: PHYSIOLOGICAL AND PATHOLOGICAL IMPLICATIONS IN PAEDIATRIC ENDOCRINOPATHIES
Capalbo, Donatella (2009) CROSS-TALK BETWEEN ENDOCRINE SYSTEM AND OTHER BIOLOGICAL PATHWAYS: PHYSIOLOGICAL AND PATHOLOGICAL IMPLICATIONS IN PAEDIATRIC ENDOCRINOPATHIES. [Tesi di dottorato] (Inedito)
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Endocrine system exerts relevant effects on multiple organs and tissues. Pleiotropic and redundant functions of circulating hormones are due to the various receptors expressed on multiple target cells. Moreover, receptors of circulating hormones share common transducing elements with receptors of many other molecules. Consequently, endocrine system participate to an integrated network of mediators that communicate and coordinate responsive cells to achive effective functions in an appropriate fashion. The presence of such a complex interplay contribute to unravel previously unappreciated functions of circulating hormones and the mechanisms of coordination and integration of several pathways. An example of this interplay is the complex interaction between endocrine and immune system. Cytokines and growth factors, in fact, after their binding to cell-surface receptos, activate common intracytoplasmatic signaling molecules. In the recent years the description of complex phenotypes, in which immunodeficiency and growth failure were associated at a different extent, greatly contributed to define how several signaling molecules play a role in both systems. As well as immunodeficiency, autoimmune diseases represent a unique model to study interactions between endocrine and immune systems. Cardiovascular system also represents a biological system higly sensitive to the effects of circulating hormones as suggested by the presence of several cardiovascular and metabolic alterations found in many endocrine diseases. In fact, patient with growth hormone deficiency as well as thyroid dysfunction, may present an increased morbidity due to cardiovascular events and an increased incidence of atherosclerosis. Aim of this project was to evaluate physiological and pathological implications of these complex molecular interactions on paediatric endocrinopathies starting from complex phenotype involving endocrine and other biological systems. To this aim, we started from the study of 3 model of complex diseases: • The model of autoimmune diseases • The model of Growth Hormone (GH) Deficiency (GHD) • The model of Congenital Hypothyroidism (CH) Moreover, during the study of patients affected with Growth Hormone and thyroid disorders we also identified new genetic causes of GH deficiency and hyperthyroidism, highlithing new insights in the genetics of endocrine diseases, as described in the last chapter of the thesis.
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