Aldosterone Metabolism in Rat Renal Tissue in Vitro. Formation of Lipid Soluble Metabolites

Overview

Journal Pflugers Arch

Specialty Physiology

Date 1988 May 1

PMID 3387188

Citations 1

Authors

D lAllemand

H Siebe

D Tsiakiras

G A Hoyer

P Vecsei

K HIERHOLZER

Affiliations

Soon will be listed here.

Abstract

In the present study the formation of lipid soluble metabolites from 3H-aldosterone was investigated in vitro in isolated kidneys and kidney and liver slices of Sprague Dawley rats. The steroids were separated by HPLC (forward and reversed phase systems) and detected on-line as UV- or 3H-chromatograms. Apart from an unenzymatically formed substance, isoaldosterone, three less polar metabolites were traced (A1, A2, A3). The structure of the quantitatively most important metabolite (A1), was identified as 5 alpha-dihydroaldosterone using a combination of techniques such as chromatographic comparison with reference steroids, antibody binding and mass spectrometry. Evidence for further conversion of DHaldo to 3 alpha, 5 alpha-tetrahydroaldosterone was obtained in chromatographic and antibody binding studies. The formation of metabolites was not dependent on glomerular filtration. Furthermore it displayed regional heterogeneity with highest activity in the outer medulla. Finally it was observed that the in vitro metabolism of aldosterone was not saturable over a range of initial aldo concentration of 10(-9) to 10(-5) M.

Citing Articles

Bile acids and their amidates inhibit 11 beta-hydroxysteroid dehydrogenase obtained from rat kidney.

Perschel F, Buhler H, HIERHOLZER K Pflugers Arch. 1991; 418(6):538-43.

PMID: 1945747 DOI: 10.1007/BF00370568.

References

MCCAA C, Sulya L . Pathways of excretion of 3H-1,2-d-aldosterone radiometabolites in the rat. Endocrinology. 1966; 79(4):815-8. DOI: 10.1210/endo-79-4-815. View

Ulick S, LARAGH J, Lieberman S . The isolation of a urinary metabolite of aldosterone and its use to measure the rate of secretion of aldosterone by the adrenal cortex of man. Trans Assoc Am Physicians. 1958; 71:225-35. View

Flood C, PINCUS G, Tait J, TAIT S, Willoughby S . A comparison of the metabolism of radioactive 17-isoaldosterone and aldosterone administered intravenously and orally to normal human subjects. J Clin Invest. 1967; 46(5):717-27. PMC: 297074. DOI: 10.1172/JCI105572. View

Ulick S . Stereospecificity in the metabolism of aldosterone in man. J Biol Chem. 1961; 236:680-4. View

Morris D . Further studies on aldosterone metabolism. The Claude P. Brown memorial lecture. Ann Clin Lab Sci. 1986; 16(2):94-102. View

Kohler H, HESSE R, PECHET M . THE METABOLISM OF ALDOSTERONE. METABOLIC PATHWAY, ISOLATION, CHARACTERIZATION, AND SYNTHESIS OF METABOLITES. J Biol Chem. 1964; 239:4117-23. View

Morris D . The metabolism and mechanism of action of aldosterone. Endocr Rev. 1981; 2(2):234-47. DOI: 10.1210/edrv-2-2-234. View

Rossier B, Wilce P, Edelman I . Kinetics of RNA labeling in toad bladder epithelium: effects of aldosterone and related steroids. Proc Natl Acad Sci U S A. 1974; 71(8):3101-5. PMC: 388629. DOI: 10.1073/pnas.71.8.3101. View

KIRK D, Miller B . 18-substituted steroids--9[1]. Studies on the stability of aldosterone in dilute alkali. J Steroid Biochem. 1982; 16(2):269-76. DOI: 10.1016/0022-4731(82)90175-3. View

10.

McDermott M, Latif S, Morris D . The metabolism of aldosterone in kidney. J Steroid Biochem. 1983; 19(2):1205-11. DOI: 10.1016/0022-4731(83)90418-1. View

11.

KELLY W, BANDI L, Lieberman S . ISOLATION AND CHARACTERIZATION OF HUMAN URINARY METABOLITES OF ALDOSTERONE. V. DIHYDROALDOSTERONE AND 21-DEOXYTETRAHYDROALDOSTERONE. Biochemistry. 1963; 2:1249-54. DOI: 10.1021/bi00906a013. View

12.

Farman N, Bonvalet J . Aldosterone binding in isolated tubules. III. Autoradiography along the rat nephron. Am J Physiol. 1983; 245(5 Pt 1):F606-14. DOI: 10.1152/ajprenal.1983.245.5.F606. View

13.

Schurek H, Brecht J, Lohfert H, HIERHOLZER K . The basic requirements for the function of the isolated cell free perfused rat kidney. Pflugers Arch. 1975; 354(4):349-65. DOI: 10.1007/BF00587852. View

14.

Connolly T, Vecsei P, Haack D, Kohl K, Abdelhamid S, Ammenti A . Aldosterone diagnosis in hypertension: comparative evaluation of radioimmunoassays for urinary aldosterone and 18-OH-corticosterone. Klin Wochenschr. 1978; 56 Suppl 1:173-81. DOI: 10.1007/BF01477470. View

15.

Sandor T, Lanthier A . The metabolism of aldosterone. II. Acta Endocrinol (Copenh). 1962; 39:87-102. DOI: 10.1530/acta.0.0390087. View

16.

Farman N, Pradelles P, Bonvalet J . Binding of aldosterone metabolites in isolated tubular segments. Am J Physiol. 1985; 249(6 Pt 2):F923-32. DOI: 10.1152/ajprenal.1985.249.6.F923. View

17.

Brien T, Slater J . Isomerization of radioactive aldosterone at C-17: enzymic purification of the 17-alpha- and beta-isomers. J Endocrinol. 1967; 38(2):197-8. DOI: 10.1677/joe.0.0380197. View

18.

Kobayashi N, Schulz W, HIERHOLZER K . Corticosteroid metabolism in rat kidney in vitro. IV. Subcellular, sites of 11 beta-hydroxysteroid dehydrogenase activity. Pflugers Arch. 1987; 408(1):46-53. DOI: 10.1007/BF00581839. View

19.

KELLY W, BANDI L, Lieberman S . ISOLATION AND CHARACTERIZATION OF HUMAN URINARY METABOLITES OF ALDOSTERONE. IV. THE SYNTHESIS AND STEREOCHEMISTRY OF TWO BICYCLIC ACETAL METABOLITES. Biochemistry. 1963; 2:1243-9. DOI: 10.1021/bi00906a012. View

20.

DECK K, SIEGENTHALER W . Further experimental evidence for the formation of the acid hydrolyzable conjugate of aldosterone by the kidney. Acta Endocrinol (Copenh). 1967; 55(4):637-47. DOI: 10.1530/acta.0.0550637. View