Glucocorticoids are known to modulate immunological processes by influence of development and effector functions of immune system. The ability of the cells to respond to glucocorticoid hormones depends not only on their plasma concentration, the responsiveness of the target cells but also on the expression of their receptors and local metabolism of glucocorticoids that is predominated by 11b-hydroxysteroid dehydrogenases type 1 and 2 (11b-HSD1, 11b-HSD2). 11b-HSD2 operates strictly as an oxidase that converts biologically active glucocorticoids (cortisol, corticosterone) to their inactive 11-keto forms (cortisone, 11-dehydrocorticosterone) whereas 11b-HSD1 reduces predominantly the 11-keto forms to active glucocorticoids. It is suggested that NADPH, which is used by 11b-HSD1 to function as a reductase, is generated by hexose-6-phosphate dehydrogenase (H6PDH) in the lumen of endoplasmic reticulum. Because evidence suggests that glucocorticoids play essential roles during development and differentiation of some kinds of immune cells, the aim of our study was to determine whether the developmental changes of immune organs are accompanied with changes of the local metabolism of glucocorticoids. We studied, therefore, the expression of 11b-HSD1 and H6PDH in immune organs like thymus, spleen, and lymph nodes and in liver of Wistar male rats during suckling, weaning, prepubertal and adult period of life. The abundance of mRNAs was measured by qRT-PCR using TaqMan probes. PCR reaction was performed as a duplex measurement of the gene of interest and the housekeeping gene (GAPDH). Splenic and hepatic 11b-HSD1 mRNA levels were increasing significantly during suckling and weaning period and the highest values reached in adulthood. In contrast, 11b-HSD1 transcript in thymus and lymphatic nodes decreased after weaning. The abundance of H6PDH mRNA increased in spleen and liver of sucklings and weanlings, was not changed in thymus and decreased in lymphatic nodes. In adulthood, the levels of H6PDH mRNA were higher than in early postnatal life only in spleen, and lower in liver and lymphatic nodes. These results show that the developmental patterns of both enzymes are different in the investigated organs and that the capacity of the local metabolism of glucocorticoids might be on different levels during ontogeny.

The project was supported by Czech Science Foundation GACR 305/07/0328.