Intrathymic somatotropic circuitry: consequences upon thymus involution

Abstract

Growth hormone (GH) is a classic pituitary-derived hormone crucial to body growth and metabolism. In the pituitary gland, GH production is stimulated by GH-releasing hormone and inhibited by somatostatin. GH secretion can also be induced by other peptides, such as ghrelin, which interacts with receptors present in somatotropic cells. It is well established that GH acts directly on target cells or indirectly by stimulating the production of insulin-like growth factors (IGFs), particularly IGF-1. Notably, such somatotropic circuitry is also involved in the development and function of immune cells and organs, including the thymus. Interestingly, GH, IGF-1, ghrelin, and somatostatin are expressed in the thymus in the lymphoid and microenvironmental compartments, where they stimulate the secretion of soluble factors and extracellular matrix molecules involved in the general process of intrathymic T-cell development. Clinical trials in which GH was used to treat immunocompromised patients successfully recovered thymic function. Additionally, there is evidence that the reduction in the function of the somatotropic axis is associated with age-related thymus atrophy. Treatment with GH, IGF-1 or ghrelin can restore thymopoiesis of old animals, thus in keeping with a clinical study showing that treatment with GH, associated with metformin and dehydroepiandrosterone, could induce thymus regeneration in healthy aged individuals. In conclusion, the molecules of the somatotrophic axis can be envisioned as potential therapeutic targets for thymus regeneration in age-related or pathological thymus involution.

Somatostatin Receptor Gene Functions in Growth Regulation in Bivalve Scallop and Clam

“…The insulin and IGF signaling pathways are crucial regulators of glucose, lipid, and protein metabolism [27,28]. In vertebrates, SSTR negatively regulates growth via the suppression of growth hormone and IGF-1 [29,30]. Fish SSTR-6 was shown to inhibit the expression of the IGF gene, which then reduced the speed of liver metabolism, thus inhibiting growth [22].…”

Brain-Thymus connections in Chagas Disease

“…In addition to GH, other hormones of the somatotropic axis as IGF-1, ghrelin, and somatostatin are expressed in the thymus, where they are involved in the general process of intrathymic T-cell development [71]. IGF-1 mediates a large number of the effects of GH upon the thymus: the enhancing effects of GH upon thymulin production, extracellular matrix expression, and adhesion of developing thymocytes to TECs can be abrogated by treating cells with anti-IGF-1 and IGF-1R antibodies [69].…”