11β-hydroxysteroid dehydrogenase type 1 (11HSD1) is an enzyme that amplifies intracellular glucocorticoid concentration by the conversion of inert glucocorticoids to active forms and is involved in the interconversion of 7-oxo- and 7-hydroxy-steroids, which can interfere with the activation of glucocorticoids. The presence of 11HSD1 in the structures of the hypothalamic-pituitary-adrenal (HPA) axis suggests that this enzyme might play a role in the regulation of HPA output. Here we show that the exposure of Fisher 344 rats to mild social stress based on the resident-intruder paradigm increased the expression of 11HSD1 and CYP7B1, an enzyme that catalyzes 7-hydroxylation of steroids. We found that social behavioral profile of intruders was significantly decreased whereas their plasma levels of corticosterone were increased more than in residents. The stress did not modulate 11HSD1 in the HPA axis (paraventricular nucleus, pituitary, adrenal cortex) but selectively upregulated 11HSD1 in some regions of the hippocampus, amygdala and prelimbic cortex. In contrast, CYP7B1 was upregulated not only in the hippocampus and amygdala but also in paraventricular nucleus and pituitary. Furthermore, the stress downregulated 11HSD1 in the thymus and upregulated it in the spleen and mesenteric lymphatic nodes whereas CYP7B1 was upregulated in all of these lymphoid organs. The response of 11HSD1 to stress was more obvious in intruders than in residents and the response of CYP7B1 to stress predominated in residents. We conclude that social stress induces changes in enzymes of local metabolism of glucocorticoids in lymphoid organs and in brain structures associated with the regulation of the HPA axis. In addition, the presented data clearly suggest a role of 11HSD1 in modulation of glucocorticoid feedback of the HPA axis during stress.

• MeSH
• 11-beta-Hydroxysteroid Dehydrogenase Type 1 metabolism   MeSH
• Behavior, Animal physiology   MeSH
• Corticosterone blood   MeSH
• Rats MeSH
• Brain enzymology   MeSH
• Rats, Inbred F344 MeSH
• Stress, Psychological blood   enzymology   MeSH
• Cytochrome P450 Family 7 MeSH
• Social Behavior * MeSH
• Steroid Hydroxylases metabolism   MeSH
• Pituitary-Adrenal System metabolism   MeSH
• Hypothalamo-Hypophyseal System metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• 11-beta-Hydroxysteroid Dehydrogenase Type 1 MeSH
• Cyp7b1 protein, rat MeSH Browser
• Corticosterone MeSH
• Cytochrome P450 Family 7 MeSH
• Steroid Hydroxylases MeSH