Effects of Intraperitoneal Administration of Mifepristone on Glucocorticoid Status of Experimental Animals.

We studied the content of corticosterone and its precursors in the adrenal glands, corticosterone in blood serum and daily urine of rats, and activity of first and second isoforms of 11β-hydroxysteroid dehydrogenase in the liver and kidneys of rats after 15 daily intraperitoneal injections of 0.9% NaCl or glucocorticoid receptor blocker mifepristone in 0.9% NaCl. Daily injections of NaCl reduced the levels of pregnenolone, progesterone, and corticosterone in the adrenal glands, increased corticosterone excretion with urine, enhanced activity of the first isoform of 11β-hydroxysteroid dehydrogenase in the liver and reduction in activity of the second isoform of this enzyme in the kidneys. These changes are typical manifestations of chronic stress. Mifepristone restored pregnenolone content in the adrenal glands and increase in corticosterone concentration in the blood. Under these conditions, activity of the first isoform of 11β-hydroxysteroid dehydrogenase in the liver did not change, and a decrease in activity of the second isoform of the enzyme in the kidneys was less pronounced. The results suggest that mifepristone abolished the stress-mediated increase in activity of the first isoform of 11β-hydroxysteroid dehydrogenase in the liver and reduced local production of glucocorticoid hormones and their metabolic effects in hepatocytes.