Skip to main content
SpringerLink
Log in

Corticosteroid metabolism in isolated rat kidney in vitro

I. Formation of lipid soluble metabolites from corticosterone (B) in renal tissue from male rats

  • Transport Processes, Metabolism and Endocrinology; Kidney, Gastrointestinal Tract, and Exocrine Glands
  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Abstract

Kidneys of male Sprague Dawley rats have been isolated and perfused in vitro in order to study the metabolism of corticosterone (B). B is the main endogenous corticosteroid in this species. Using3H-B and HPLC for the separation of steroid metabolites it has been possible to detect radioactive derivatives of B which have been denoted as met I, II and III. These substances were purified and compared with authentic reference hormones under different isocratic and gradient elution techniques. We observed chromatographic identity of met I with 11-dehydro-20-dihydro-B, of met II with 20-dihydro-B and of met III with 5α-H-4,5-dihydro-B. From the fact that conversion of B can be observed with normal (50 g · l−1 albumin in perfusate) and elevated (75 g · l−1) colloid osmotic pressure of the recirculating perfusate it can be concluded that B gets access to the metabolic site in renal tissue not solely by glomerular filtration and tubular reabsorption. The metabolites identified presently are excreted in the urine. Metopirone increased the concentration of met I and decreased the concentration of met II. This is compatible with the concept of a stimulatory effect of metopirone on a C-20-hydroxysteroid oxidoreductase and a C-11-hydroxysteroid dehydrogenase.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

aldo:

aldosterone

B:

corticosterone

3H-B:

(1,2,6,7-3H)-corticosterone

CS:

corticosteroid

HPLC:

high pressure liquid chromatography

met I (II, III):

metabolite I (II, III)

P:

perfusate

U:

urine

KH:

kidney homogenate

MS:

mass spectrometry

ESR:

external standard ratio

n-hex:

n-hexane (spectrograde)

isoprop:

Isopropanol (spectrograde)

References

  1. Amamoo D (1968) Über den Einfluß anaboler C19-Steroide auf den Corticosteron-Stoffwechsel der Ratte in vivo. Inaugural-Dissertation, Freie Universität Berlin

  2. Baer PG, McGiff JC (1980) Hormonal systems and renal hemodynamics. Ann Rev Physiol 42:589–601

    Google Scholar 

  3. Bush IE (1953) Species differences in adrenocortical secretion. J Endocrinol 9:95–100

    Google Scholar 

  4. Deck KA, Siegenthalter WE (1967) Further experimental evidence for the formation of the acid hydrolyzable conjugate of aldosterone by the kidney. Acta Endocrinol 55:637–647

    Google Scholar 

  5. DeLuca HF (1981) Recent advances in the metabolism of vitamin D. Ann Rev Physiol 43:199–209

    Google Scholar 

  6. DeMello G, Maack T (1976) Nephron function of the isolated perfused rat kidney. Am J Physiol 231:1699–1707

    Google Scholar 

  7. Emmanouel DS, Lindheimer MD, Katz AI (1980) Role of the kidney in hormone metabolism and its implications in clinical medicine. Klin Wochenschr 58:1005–1012

    Google Scholar 

  8. Erickson RE, Ertel RJ, Ungar F (1966) Effect of SU-4885 on steroid 18-hydroxylation in the mouse adrenal in vitro. Endocrinol 78:343–349

    Google Scholar 

  9. Fröhlich JC, Nies AS, Schrier RW (guest eds) (1981) Prostglandins and the kidney. Kidney Int 19:775–880

  10. Hierholzer K, Tsiakiras D, Schöneshöfer M, Siebe H, Weskamp P (1981) Renal handling of hormones. In: Greger R, Lang F, Silbernagl S (eds). Springer, Berlin Heidelberg New York, pp 278–289

    Google Scholar 

  11. Hierholzer K, Lichtenstein I, Siebe H, Tsiakiras D, Witt I (1982) In vitro conversion of corticosterone (B) by rat renal tissue. Biochem of kidney functions. INSERM Symp. No. 21, Morel F (ed). Elsevier Biomedical Press. Amsterdam, pp 233–240

    Google Scholar 

  12. Hierholzer K, Lichtenstein I, Siebe H, Tsiakiras D, Witt I (1982) Renal metabolism of corticosteroid hormones. Klin Wochenschr 60:1127–1135

    Google Scholar 

  13. Horton R, Dunn MJ (eds) (1981) Prostaglandins and the kidney. Mineral and Electrolyte Metab 6:5–104

    Google Scholar 

  14. Levin J, Barnett Z, Fukushima DK (1978) Extraadrenal effects of metopirone in man. J Clin Endocrinol Metab 47:845–849

    Google Scholar 

  15. Liddle GW, Island D, Lance EM, Harris AP (1958) Alterations of adrenal steroid patterns in man resulting from treatment with a chemical inhibitor of 11-hydroxylase. J Clin Endocrinol metab 18:906–912

    Google Scholar 

  16. Lisboa BP, Landgraf M, Leichtweiss HP (1981) Use of gasliquid chromatography with radioactive detection in the study of the metabolism of 4-14C testosterone in the isolated and artificially perfused rat kidney. Figerio A (ed) Chromatogr in biochemistry, medicine and environmental, vol. 1. Elsevier Comp, Amsterdam, pp 261–287

    Google Scholar 

  17. Llaurado JG, Claus JL, Trunell JB (1962) Aldosterone excretion in feces of rats treated with estradiol. Endocrinol 71:598–604

    Google Scholar 

  18. Maack T, Johnson V, Kau ST, Figueiredo J, Sigulem D (1979) Renal filtration, transport, and metabolism of low molecularweight proteins. A review. Kidney Int 16:251–270

    Google Scholar 

  19. McCaa R, McCaa CS, Read DG, Bower JD, Guyton AC (1972) Increased plasma aldosterone concentration in response to haemodialysis in nephrectomized man. Circ Res 31:473–480

    Google Scholar 

  20. Möhring J, Möhring B, Siegenthaler W (1968) Die biologische Aktivität von Tetrahydroaldosteron, Tetrahydroaldosteronglucuronid und 18-Aldosteronglucuronid im Vergleich mit Aldosteron. Klin Wschr 46:22–24

    Google Scholar 

  21. Nakane H, Nakane Y, Reach G, Corvol P, Menard J (1978) Aldosterone metabolism in isolated perfused rat kidney. Am J Physiol 234:E472-E479

    Google Scholar 

  22. Nasjletti A, Malik KU (1981) The renal kallikrein-kinin and prostaglandin systems interaction. Ann Rev Physiol 43:597–609

    Google Scholar 

  23. Neudert W, Röpke H (1965) Steroid-Spektrenatlas. Springer, Berlin Heidelberg New York

    Google Scholar 

  24. Poralla T (1979) Vergleich des Einflusses von Albumin und Heemaccel als Kolloid auf die Funktion isoliert perfundierter Rattennieren (Elektrolytausscheidung und Reininsystem). Med Diss. Freie Universität Berlin

  25. Reach G, Nakane H, Nakane Y, Auzan C, Corvol P (1977) Cortisol metabolism and excretion in the isolated perfused rat kidney. Steroids 30:621–635

    Google Scholar 

  26. Seth P (1969) Occurrence and function of corticosteroids in some selected mammalian species. Gen Comp Endocrinol [Suppl] 2:317–324

    Google Scholar 

  27. Siebe H, Tsiakiras D, Hierholzer K, with technical assistance of Lichtenstein I (1984) Corticosteroid metabolism in isolated rat kidney in vitro. II. Sex dependency of metabolism and formation of 11-dehydro-corticosterone. Pflügers Arch 400: 372–376

    Google Scholar 

  28. Schöneshöfer M, Dulce HJ (1979) Comparison of different high-performance liquid chromatographic systems for the purification of adrenal and gonadal steroids prior to immunoassay. J Chromatogr 164:17–28

    Google Scholar 

  29. Schöneshöfer M, Fenner A (1981) A convenient and efficient method for the extraction and fractionation of steroid hormones from serum or urine. J Clin Chem Clin Biochem 19:71–74

    Google Scholar 

  30. Schöneshöfer M, Fenner A, Dulce HJ (1981) Assessment of eleven adrenal steroids from a single serum sample by combination of automatic high-performance liquid chromatography and radio-immunoassay. J Steroid Biochem 14:377–386

    Google Scholar 

  31. Schöneshöfer M, Weber B, Nigam S (1983) Increased urinary excretion of free 20α- and 20β-dihydrocortisol in a hypercortisolemic but hypocortisoluric patient with Cushing's disease. Clin Chemistry 29:385–389

    Google Scholar 

  32. Schurek HJ, Brecht JP, Lohfert H, Hierholzer K (1975) The basic requirements for the function of the isolated cell free perfused rat kidney. Pflügers Arch 354:349–365

    Google Scholar 

  33. Thurau K, Schnermann J (guest eds) (1982) The juxta-glomerular apparatus. Kidney Int Suppl 12, Proc Sat Symp of VIII Int Congr of Nephrol, Athens, 1981

  34. Tsiakiras D, Siebe H, Weskamp P, Hierholzer K (1981) Metabolic conversion of3H-corticosterone (CS) by the isolated perfused rat kidney. Pflügers Arch 389:R42

    Google Scholar 

  35. Tsiakiras D (1982) Corticosteronmetabolismus in der isoliert perfundierten Niere der Ratte. Inaugural-Dissertation, Freie Universität Berlin

  36. Winkel CA, Simpson ER, Milewich L, MacDonald PC (1981) Deoxycorticosterone biosynthesis in human kidney: Potential for formation of a potent mineralo-corticosteroid in its site of action. Proc Natl Acad Sci USA 77:7069–7073

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Klinische Physiologie, Klinikum Steglitz der Freien Universität Berlin, Hindenburgdamm 30, D-100, Berlin 45

    K. Hierholzer, M. Schöneshöfer, H. Siebe, D. Tsiakiras, P. Weskamp & Ingrid Lichtenstein

Authors
  1. K. Hierholzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Schöneshöfer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Siebe
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Tsiakiras
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. Weskamp
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ingrid Lichtenstein
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hierholzer, K., Schöneshöfer, M., Siebe, H. et al. Corticosteroid metabolism in isolated rat kidney in vitro. Pflugers Arch. 400, 363–371 (1984). https://doi.org/10.1007/BF00587533

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00587533

Key words

Search

Navigation