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On the mechanism of the inhibitory action of the spirolactone SC 9376 (aldadiene) on the production of corticosteroids in rat adrenals in vitro

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Summary

Quartered adrenals of normally fed and of sodium-deficient rats were incubated with and without the addition of stimulators of corticosteroid biosynthesis. The addition of spirolactone SC 9376 (aldadiene), 5×10−6–10−4 M, inhibited the production of corticosterone, 18-hydroxydesoxycorticosterone, 18-hydroxycorticosterone and aldosterone in a dose-dependent manner. The inhibitory effect of spironolactone (SC 9420) on corticosterone production was less pronounced than that of aldadiene.

After incubation of adrenal tissue with aldadiene, polar metabolites of aldadiene were detected in the tissue as well as in the incubation medium. The production of the aldadiene metabolites increased with the aldadiene concentration in the medium and was reduced by a simultaneous stimulation of corticosteroid synthesis. The mass spectrometric analysis of two aldadiene metabolites revealed a hydroxylation of aldadiene in two different positions, probably at the carbon in position 11 and 18, respectively.

From the results it is concluded that the inhibition of synthesis of the investigated corticosteroids is due to competition between aldadiene and intermediates of the corticosteroid biosynthesis for mitochondrial hydroxylases.

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References

  • Cella, J. A.: Chemistry and structure-activity relationships of some steroidal spirolactones. In: Edema, mechanism and management, p. 303. Ed. by J. H. Moyer and M. Fuchs. Philadelphia-London: W. B. Saunders 1960.

    Google Scholar 

  • Davis, D. A., Medline, N. M.: Spironolactone (aldactone) bodies: Concentric lamellar formation in the adrenal cortices of patients treated with spironolactone. Amer. J. clin. Path. 54, 22–32 (1970).

    Google Scholar 

  • Eistert, B., Regitz, M., Heck, G., Schwall, H.: Aliphatische Diazoverbindungen. In: Houben-Weyl: Methoden der Organischen Chemie, Band X/4, S. 552–553. Stuttgart: G. Thieme 1968.

    Google Scholar 

  • Erbler, H.: Stimulation of aldosterone production in vitro and its inhibition by spironolactone. Naunyn-Schmiedeberg's Arch. Pharmacol. 273, 366–375 (1972).

    Google Scholar 

  • Fisher, E. R., Horvat, E.: Experimental production of so-called spironolactone bodies. Arch. Path. 91, 471–478 (1971a).

    Google Scholar 

  • Fisher, E. R., Horvat, B.: Ultrastructural features of Aldosterone production. Arch. Path. 92, 172–179 (1971b).

    Google Scholar 

  • Gláz, E., Sugár, K.: New viewpoints in the use of progesterone in the treatment of cardiac oedemas associated with secondary hyperaldosteronism. Ther. hung. 12, 105 (1964).

    Google Scholar 

  • Gochman, N., Gantt, C. L.: A fluorimetric method for the determination of a major spironolactone (aldactone) metabolite in human plasma. J. Pharmacol. exp. Ther. 135, 312 (1962).

    Google Scholar 

  • Janigan, D. T.: Cytoplasmic bodies in the adrenal cortex of patients treated with spirolactone. Lancet 1963 I, 850–852.

    Google Scholar 

  • Jenis, E. H., Hertzog, R. W.: Effect of spironolactone on the zona glomerulosa of the adrenal gland: Light and electron microscopy. Arch. Path. 88, 530–539 (1969).

    Google Scholar 

  • Kittinger, G. W.: Quantitative gas chromatography of 17-deoxycorticosterone and other steroids produced by the rat adrenal gland. Steroids 3, 21–42 (1964).

    Google Scholar 

  • Merits, I.: Gas liquid chromatography of adrenal cortical steroid hormones. J. Lipid Res. 3, 126–127 (1962).

    Google Scholar 

  • Moeller, J.: Aldosteron und Aldosteronantagonisten. In: Abhandlungen über die Pathophysiologie der Regulationen, Heft 14. Jena: VEB G. Fischer 1969.

    Google Scholar 

  • Solymoss, B., Tóth, S., Varga, S., Krajny, M.: The influence of spironolactone on its own biotransformation. Steroids 16, 263–275 (1970).

    Google Scholar 

  • Stahl, F., Hertling, I., Knappe, G.: Eine einfache fluorometrische Methode zur Routinebestimmung von Corticosteroiden in kleinen Plasmamengen. Acta biol. med. germ. 10, 480–487 (1963).

    Google Scholar 

  • Wagner, H., Weist, F., Zicha, L.: Aldadien und andere Metaboliten im Blut und Harn nach rectaler Applikation von Spironolacton und intravenöser Injektion von Aldadien-Kalium. Arzneimittel-Forsch. 17, 415–419 (1967).

    Google Scholar 

  • Werning, C.: Das Renin-Angiotensin-Aldosteron-System. Stuttgart: G. Thieme 1972.

    Google Scholar 

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Erbler, H.C. On the mechanism of the inhibitory action of the spirolactone SC 9376 (aldadiene) on the production of corticosteroids in rat adrenals in vitro. Naunyn-Schmiedeberg's Arch. Pharmacol. 277, 139–149 (1973). https://doi.org/10.1007/BF00501155

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