Glucocorticoid production in the murine thymus

Glucocorticoid hormones are known to act as important modulatory factors in the development of autoimmune diseases, and to play an important role in t hymic T-cell selection. There seems to be a finely balanced equilibrium bet ween the apoptosis-inducing effects of glucocorticoid and T cell receptor l igand binding. Here we are investigating whether glucocorticoid-induced T c ell apoptosis is mainly dependent on circulating glucocorticoid levels or i f the thymus itself is able to produce glucocorticoids. To this end, we att empted to demonstrate enzyme activities of the whole set of steroidogenic e nzymes for the synthesis of glucocorticoids in murine thymic tissue. We iso lated steroidogenic organelles from thymic tissue, incubated these with rad ioactive (precursor) steroids in vitro, and visualized the resulting produc ts by thin-layer chromatography Our results show that the thymus possesses all enzymes and cofactors required for glucocorticoid production. However, an intact thymic architecture is necessary for glucocorticoid production, s ince 11 beta-hydroxylase was not detected in irradiated thymi or in a thymi c epithelial cell line. The results of these experiments show that the whol e glucocorticoid metabolism takes place within the thymus. This finding pro vides the biochemical basis for the in situ effects of glucocorticoid hormo nes on thymocyte development and selection.