Endocrine Abstracts

Stressful experiences produce profound physiological and behavioural disturbances that may contribute to many psychiatric disorders. Stress activates HPA axis whose end products glucocorticoids modulate immune cells and cytokine activity. Local effect of glucocorticoids depends not only on its concentration but also on the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11HSD1), which amplifies intracellular glucocorticoid concentration by the conversion of inactive 11-dehydrocorticosterone to active corticosterone. As cytokines are potent modulators of 11HSD1, it was interested to establish whether cytokines could modulate metabolism of glucocorticoids in response to various stressors. Fisher 344 rats were exposed to chronic emotional homotypic stress (resident-intruder paradigm) or short-term variable stress combining emotional and physical stressors. Plasma level of corticosterone, TNFα and IL1β were measured by commercial kits, expression of 11HSD1, TNFα, and IL1β mRNAs by RT-PCR and 11-reductase activity by radiometric assay. We found that long-term homotypic stress increased corticosterone and decreased TNFα and IL1β in plasma. Expression of 11HSD1 mRNA was increased in thymus and spleen but not in mesenteric lymph nodes and liver. Similar pattern was found in expression of TNFα and IL1β – both cytokines were upregulated in thymus and spleen but not in liver and lymph nodes. Stimulatory effect of stress on 11-redutase activity was observed in both mobile cells and stroma of all three lymphoid organs. Vagotomy did not affect the stress-dependent upregulation of 11HSD1 in spleen and mesenteric lymph nodes. In contrast to chronic stress, the short-term variable stress up-regulated 11HSD1 only in thymus but not in spleen and lymph nodes. The findings demonstrate that a powerful stressor may have strong effect on glucocorticoid signaling in some peripheral organs, in particular lymphoid, but the nature of the effect varies with the specificity of stress and tissue. In lymphoid organs, the stressful episodes increase 11HSD1 in parallel with upregulation of TNFα and IL1β, which have been shown previously to stimulate 11HSD1 in vitro.

Disclosure: This work was supported by the Czech Science Foundation (grant numbers 15-07268S and P303/10/0969).