Thymus-derived glucocorticoids are insufficient for normal thymus homeostasis in the adult mouse

A clear relationship was observed between systemic corticosterone concentration, thymus cell number, and percentage of apoptotic thymocytes. Physiological concentrations of corticosterone in adrenalectomized mice restored thymus cell number to normal values and revealed differential sensitivity of thymocyte subpopulations to physiological and stress-inducible corticosterone concentrations.This indicates that thymus-derived glucocorticoids are not sufficient to maintain normal levels of death by neglect in the thymus, but that apoptosis and possibly other mechanisms induced by physiological, non stress-induced levels of adrenal-derived corticosterone are responsible for keeping the total number of thymocytes within the normal range.Although it is clear that elevated concentrations of endogenous glucocorticoids can cause apoptosis in the thymus [1-3], the role of normal concentrations of glucocorticoids in thymic homeostasis remains controversial [4-7]. Results reported by Ashwell and colleagues suggest glucocorticoids are essential at very low concentrations for early development and survival of thymocytes and that glucocorticoids can alter the sensitivity of more mature thymocytes to positive selection, thereby influencing the T cell receptor repertoire [5]. In addition, there is convincing evidence that corticosterone is produced in the thymus and that it acts locally to affect thymocyte development [8,9]. Therefore, it was surprising when normal cellular development (including repertoire) was observed until the time of birth in glucocorticoid receptor knockout mice [10]. This raised serious questions about the necessity of glucocorticoids as a required or permissive agent in thymic development.It has also been suggested that glucocorticoids play a role in homeostasis in the adult thymus by inducing death by neglect of thymocytes that are neither positively nor negatively selected. This idea has been based on the observation that the predominant cell type subjected