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

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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.

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References

  1. G. A. Melnichenko, I. I. Dedov, Zh. E. Belaya, L. Ya. Rozhinskaya, G. R. Vagapova, N. I. Volkova, A. Yu. Grigor’ev, E. N. Grineva, E. I. Marova, A. M. Mkrtumayn, Yu. Yu. Trunin, and V. Yu. Cherebillo, Cushing’s disease: the clinical features, diagnostics, differential diagnostics, and methods of treatment. Problemy Endokrinol., 61, No. 2, 55-77 (2015).

  2. N. A. Palchikova, N. V. Kuznetsova, and V. G. Selyatitskaya, Glucocorticoid function of the adrenal cortex of the rats with streptozotocin diabetes in the dynamics of mifepristone intake per os. Fundamental. Issled., No. 8-1, 100-104 (2014).

    Google Scholar 

  3. O. P. Cherkasova, The activity of 11β-hydroxysteroid dehydrogenase of rat kidney and liver at inherited stress-induced arterial hypertension. Biomed. Khimiya, 52, No. 6, 568-575 (2006).

    CAS  Google Scholar 

  4. M. E. Altuna, S. M. Lelli, L. C. San Martín de Viale, and M. C. Damasco, Effect of stress on hepatic 11beta-hydroxysteroid dehydrogenase activity and its influence on carbohydrate metabolism. Can. J. Physiol. Pharmacol., 84, No. 10, 977-984 (2006).

  5. M. S. Cooper and P. M. Stewart, 11Beta-hydroxysteroid dehydrogenase type 1 and its role in the hypothalamus-pituitaryadrenal axis, metabolic syndrome, and inflammation. J. Clin. Endocrinol. Metab., 94, No. 12, 4645-4654 (2009).

    Article  CAS  PubMed  Google Scholar 

  6. M. F. Dallman and S. Bhatnagar, Chronic Stress and Energy Balance: Role of the Hypothalamo-Pituitary-Adrenal Axis. Comprehensive Physiology, 179-210, doi: 10.1002/cphy.cp070410 (2011).

  7. N. Draper and P. M. Stewart, 11beta-hydroxysteroid dehydrogenase and the pre-receptor regulation of corticosteroid hormone action. J. Endocrinol., 186, No. 2, 251-271 (2005).

    Article  CAS  PubMed  Google Scholar 

  8. M. Fleseriu, M. E. Molitch, C. Gross, D. E. Schteingart, T. B. Vaughan 3rd, and B. M. Biller, A new therapeutic approach in the medical treatment of Cushing’s syndrome: glucocorticoid receptor blockade with mifepristone. Endocr. Pract., 19, No. 2, 313-326 (2013).

    Article  PubMed  Google Scholar 

  9. F. Gelfo, P. Tirassa, P. De Bartolo, N. Croce, S. Bernardini, C. Caltagirone, L. Petrosini, and F. Angelucci, NPY intraperitoneal injections produce antidepressant-like effects and downregulate BDNF in the rat hypothalamus. CNS Neurosci. Ther., 18, No. 6. P. 487-492 (2012).

  10. Y. D. He, C. M. Karbowski, J. Werner, N. Everds, C. Di Palma, Y. Chen, M. Higgins-Garn, S. Tran, C. A. Afshari, and H. K. Hamadeh, Common handling procedures conducted in preclinical safety studies result in minimal hepatic gene expression changes in Sprague-Dawley rats. PLoS One, 9, No. 2, doi:10.1371/journal.pone.0088750 (2014).

  11. M. Lauterburg, G. Escher, B. Dick, D. Ackermann, and F. J. Frey, Uninephrectomy reduces 11β-hydroxysteroid dehydrogenase type 1 and type 2 concomitantly with an increase in blood pressure in rats. J. Endocrinol., 214, No. 3, 373-380 (2012).

    Article  CAS  PubMed  Google Scholar 

  12. M. M. Ostrander, Y. M. Ulrich-Lai, D. C. Choi, N. M. Richtand, and J. P. Herman, Hypoactivity of the hypothalamopituitary-adrenocortical axis during recovery from chronic variable stress. Endocrinology, 147, No. 4, 2008-2017 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Institute of Experimental and Clinical Medicine, Novosibirsk, Russia

    N. A. Pal’chikova, N. V. Kuznetsova, V. G. Selyatitskaya, O. P. Cherkasova & O. I. Kuz’mina

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  1. N. A. Pal’chikova
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  2. N. V. Kuznetsova
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  3. V. G. Selyatitskaya
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  4. O. P. Cherkasova
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  5. O. I. Kuz’mina
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Correspondence to N. A. Pal’chikova.

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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 161, No. 2, pp. 218-221, February, 2016

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Pal’chikova, N.A., Kuznetsova, N.V., Selyatitskaya, V.G. et al. Effects of Intraperitoneal Administration of Mifepristone on Glucocorticoid Status of Experimental Animals. Bull Exp Biol Med 161, 257–260 (2016). https://doi.org/10.1007/s10517-016-3390-6

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  • DOI: https://doi.org/10.1007/s10517-016-3390-6

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