title: Regulation of 11β-hydroxysteroid dehydrogenase type 1 and 7α-hydroxylase CYP7B1 during social stress.
abstract: 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.
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic ; Department of Physiology, Faculty of Science, Charles University, Prague, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Vodička
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Ergang
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Anna
authors.initials: A
authors.lastname: Mikulecká
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Řeháková
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Klusoňová
authors.affiliation: Department of Physiology, Faculty of Science, Charles University, Prague, Czech Republic.
authors.forename: Jakub
authors.initials: J
authors.lastname: Makal
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Matúš
authors.initials: M
authors.lastname: Soták
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Musílková
authors.affiliation: Institute of Anatomy, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Zach
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic ; Department of Physiology, Faculty of Science, Charles University, Prague, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Pácha
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000201:enzymology*; D003345:Corticosterone / Q000097:blood; D000072474:Cytochrome P450 Family 7; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008297:Male; D010913:Pituitary-Adrenal System / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012919:Social Behavior; D013250:Steroid Hydroxylases / Q000378:metabolism*; D013315:Stress, Psychological / Q000097:blood / Q000201:enzymology*
chemical_list: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D013250:Steroid Hydroxylases; D000072474:Cytochrome P450 Family 7; C490784:Cyp7b1 protein, rat; D003345:Corticosterone