THYMIC ENDOCRINOLOGY

Thymus endocrinology is characterized by the action of various hormones on the thymus endocrine milieu consisting of thymocytes, thymic epithelial cells and thymic stromal cells. Extrathymic hormonal influences include pituitary-derived hormones, such as prolactin and indirectly by ACTH via hydrocortisone from the adrenal, by thyroid-stimulating hormone (TSH) via thyroid hormones from the thyroid, and by LH and RH via sex steroids from gonads and adrenal. In addition, the thymus produces several putative thymic hormones: thymosin-alpha-1 thymulin and thymopoietin, which have been reported to circulate and to act on both prothymocytes and mature T-cells in the periphery thus maintaining their commitment to the T-cell system and its functions. These endocrine influences decline with age and are associated with "thymic menopause" and cellular immune senescence contributing to the development of diseases in the aged, The intrathymic environment is characterized by a complex network of paracrine and autocrine endocrine signals involving both interleukins and thymic peptides. Thymic epithelial cells respond to IL-1 with proliferation and secretion of IL6 and GM-CSF. They similarly respond to cellular interactions with the production of IL1. Thymic epithelial cells also secrete thymic hormones, as exemplified by the zinc - thymulin complex, under stimulation with IL1 and other hormonal influences. Thymic stromal cells contribute, at minimum, IL1. These various interleukin and thymic hormone influences can be envisioned to operate in a synergistic interactive network to carry the evolving T-cell through its stepwise development to a mature T-cell. Further extra thymic influences regulatory for the secretory function of thymic epithelial cells and for the stepwise evolution of T-cells can be ascribed to circulating interleukins, mainly IL1 and IL2, deriving from activation and secretion of leukocytes in the periphery which act in a synergistic fashion at all levels of T-cell development via induction of high affinity IL2 receptors and the resultant IL2 dependent proliferative responses. In the future, knowledge of the molecular basis of these endocrine interactions should provide immunopharmacologic insights into new molecules and strategies for promoting T-cell development and its restoration for the treatment of a variety of T-cell immunodeficiencies ranging from aging to cancer and HIV infection.