The role of the liver in the regulation of protein-steroid interaction in healthy and irradiated animals

«Radiation and Risk», 2023, vol. 32, No. 2, pp.78-87

DOI: 10.21870/0131-3878-2023-32-2-78-87

Authors

Omelchuk N.N. – Head of Dep., Assoc. Prof., D. Sc., Biol. PFUR. Contacts: 6 Miklukho-Maklay str., Moscow, Russia, 117198. Tel.: 8-916-908-11-10; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. .
Peoples' Friendship University of Russia, Moscow

Abstract

The study of the role of the liver in the regulation of protein-steroid interaction in healthy and irradiated animals allows us to supplement a number of theoretical provisions of radiobiology on factors influencing the pathogenesis of acute radiation sickness. The relevance of the study is due to its theoretical significance in creating a holistic concept of radiobiological patterns of pathogenesis of acute radiation sickness. The aim of the experiments is to study the effect of the liver on the fractional composition of 11-oxycorticosteroids (11-OCS) in the blood plasma of healthy and irradiated animals. The experiments were carried out on 7 mongrel dogs weighing from 22 to 27 kg. In dogs, the total concentration of 11-OCS, the level of free, protein-bound and glucuronic acid-bound corticosteroids in the blood of the femoral, portal and hepatic veins were determined. At the first stage, experiments were conducted on healthy animals. 4 animals were subjected to angiostomy by skin flap method. Blood was obtained in the absence of exposure, 90 minutes after intravenous injection of 40 units of adrenocorticotropic hormone (ACTH), the introduction of hydrocortisone into the stomach at a dose of 50 or 100 mg. The total content of 11-OCS, mcg%, was determined by the fluorimetric method in the author's modification. To determine the free 11-OCS, the gel filtration method was used in the author's modification. The fraction associated with plasma proteins was isolated on a column with sephadex G-25. Glucuronides were determined after plasma incubation with beta-glucuronidase. At the second stage, the tests were carried out on irradiated animals that were exposed to -irradiation at the EGO-2 installation at an average dose rate of 5.75 Gy/min at a dose of 3.5 Gy, causing acute stage IV radiation sickness. The results of the study showed that the liver inactivates free 11-OCS, binding them to glucuronic acid. The degree of delay and inactivation of free corticoids correlate with the concentration of the latter in the blood. The liver does not affect the level of protein-related hormones. Corticosteroids bind to plasma proteins outside the liver. In acute radiation sickness, the ability of the liver to inactivate biologically active corticosteroids decreases.

Key words
acute radiation sickness, liver, blood plasma, steroid hormones, protein-steroid interaction, 11-oxycorticosteroids, glucuronic acid, angiostomy, adrenocorticotropic hormone, hydrocortisone, free hormone.

References

1. Anokhin P.K. Essays on the physiology of functional systems. Moscow, Book on Demand, 2021. 450 p. (In Russian).

2. Grebenyuk A.N., Strelova O.Yu., Legeza V.I., Stepanova E.N. Fundamentals of radiobiology and radiation medicine: textbook. St. Petersburg, LLC FOLIANT Publishing House, 2012. 232 p. (In Russian).

3. Dokshina G.A. Endocrine and metabolic aspects of radiation sickness. Tomsk, Tomsk University Publishing House, 1984. 223 p. (In Russian).

4. Moroz B.B., Kendysh I.N. Radiobiological effect and endocrine factors. Moscow, Atomizdat, 1975. 228 p. (In Russian).

5. Romantsev E.F., Blokhina V.D., Koshcheenko N.N., Filippovich I.V. Early radiation-biochemical reactions. Moscow, Atomizdat, 1966. 268 p. (In Russian).

6. Gagliardi L., Ho J.T., Torpy D.J. Corticosteroid-binding globulin: the clinical significance of altered levels and heritable mutations. Mol. Cell Endocrinol., 2010, vol. 31, no. 6, pp. 24-34.

7. Klieber M.A., Underhill C., Hammond G.L., Muller Y.A. Corticosteroid-binding globulin, a structural basis for steroid transport and proteinase-triggered release. J. Biol. Chem., 2007, vol. 282, no. 40, pp. 29594-29603.

8. Lewis J.G., Borowski K.K., Shand B.I., George P.M., Scott R.S. Plasma sex hormone-binding globulin, corticosteroid-binding globulin, cortisol, and free cortisol levels in outpatients attending a lipid disorders clinic: a cross-sectional study of 1137 subjects. Horm. Metab. Res., 2010, vol. 42, no. 4, pp. 274-279.

9. Lewis J.G., Elder P.A. Corticosteroid-binding globulin reactive center loop antibodies recognize only the intact natured protein: elastase cleaved and uncleaved CBG may coexist in circulation. J. Steroid Biochem. Mol. Biol., 2011, vol. 127, no. 3-5, pp. 289-294.

10. Zhou A., Wei Z., Stanley P.L., Read P.J., Stein P.E., Carrell R.W. The S-to-R transition of corticosteroid-binding globulin and the mechanism of hormone release. J. Mol. Biol., 2008, vol. 380, no. 1, pp. 244-251.

11. Hamrahian A.H., Oseni T.S., Arafah B.M. Measurements of serum free cortisol in critically ill patients. N. Engl. J. Med., 2004, vol. 350, no. 16, pp. 1629-1638.

12. Lewis J.G., Elder P.A. Intact or "active" corticosteroid-binding globulin (CBG) and total CBG in plasma: determination by parallel ELISAs using monoclonal antibodies. Clin. Chim. Acta, 2013, vol. 416, pp. 26-30.

13. Nguyen P.T. Lewis J.G., Sneyd J., Lee R.S., Torpy D.J., Shorten P.R. Development of a formula for esti-mating plasma free cortisol concentration from a measured total cortisol concentration when elastase-cleaved and intact corticosteroid binding globulin coexist. J. Steroid Biochem. Mol. Biol., 2014, vol. 141, pp. 16-25.

14. Vincent R.P., Etogo-Asse F.E., Dew T., Bernal W., Alaghband-Zadeh J., le Roux C.W. Serum total cortisol and free cortisol index give different information regarding the hypothalamus-pituitary-adrenal axis reserve in patients with liver impairment. Ann. Clin. Biochem., 2009, vol. 46, no. 6, pp. 505-507.

15. Yudaev N.A. Biochemistry of hormones and hormonal regulation. Moscow, Medicine, 1976. 378 p. (In Russian).

16. Berliner D., Koller H., Dougherty T. Tissue retention of cortisol and metabolites induced by ACTH: an extra adrenal effect. Endocrinology, 1961, vol. 68, pp. 621-632.

17. Guillemin R., Clayton G., Lipscomb H., Smith J. Fluorometric measurement of rat plasma and adrenal corti-costerone concentration; a note on technical details. J. Lab. Clin. Med., 1959, vol. 53, no. 5, pp. 830-832.

18. De Moor P., Hoirwegh K., Heromans G., Declerck-Raskin M.M. Protein binding of corticosteroid studied by gel filtration. J. Clin. Invest., 1962, vol. 41, no. 4, pp. 816-827.

Full-text article (in Russian)