11β-HYDROXYSTEROID DEHYDROGENASE ACTIVITY IN TISSUES OF RATS WITH CHRONIC GRANULOMATOUS INFLAMMATION
The activity of 11β-hydroxysteroid dehydrogenase (11β-HSD), a key enzyme of the pre-receptor metabolism of glucocorticoids, in the rat adrenal gland, kidney cortex and liver, as well as the content of corticosteroid hormones in the adrenal gland have been investigated in dynamics of silica induced chronic granulomatous inflammation. It was shown that levels of corticosterone and its reversible metabolite 11-dehydrocorticosterone (11DHCS) were increased in adrenal gland of experimental rats on the first day after the induction of inflammation. However content of progesterone in adrenal gland of experimental rats was two times lower than that in the control rats. On day 3 the content of corticosterone in the adrenal glands decreased; even more marked reduction of its content was observed at day 14. The content of aldosterone on the 14th day of the experiment was more than two times lower, but the content of progesterone was 2.5 times higher than in control rats, indicating that the inhibition of the final stages of corticosteroid biosynthesis pathways observed. On day 14 of the experiment the activity of 11β-HSD type 1 in the liver was increased and the activity of 11β-HSD type 2 in the kidneys was reduced, resulting in twice increase of ratio of 11β-HSD activities in the liver and kidneys. Such changes in activities of 11β-HSD isoforms made for increasing the blood corticosterone concentration under conditions of decreased synthesis this hormone in the adrenal glands. On day 22 the levels of studied parameters were returning to that of the control animals, but the content of 11DHCS in adrenal glands was decreased, indicating that its use as a substrate for the recovery of adrenal corticosterone content.