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Further studies on the mechanism of the mineralocorticoid action of licorice in humans

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Abstract

The pathogenesis of pseudohyperaldosteronism from licorice has been evaluated in 6 male volunteers taking daily 7 g of a commercial preparation of licorice for 7 days, corresponding to an intake of 500 mg/day of glycyrrhizic acid. Pseudohyperaldosteronism was evident during the treatment (increase of body weight, suppression of plasma renin activity and plasma aldosterone, reduction of serum potassium). The ratio (tetrahydro-cortisol+allo tetrahydrocortisol)/tetrahydrocortisone in urine increased in 5 cases after 3 days of treatment, without an increase of plasma mineralocorticoid activity (PMA). In the 6th case the urinary ratio was unchanged and PMA increased from the pretreatment value. After 7 days of therapy the ratio remained high and PMA was not measurable in 3 cases, while in the other 3 cases the ratio returned to pretreatment and PMA was higher than pretreatment value. We conclude that the pseudohyperaldosteronism from licorice is initially related to decreased activity of 11 μ-hydroxysteroid-dehydrogenase and afterwards also a direct effect of licorice derivatives on mineralocorticoid receptors becomes evident in some cases. In other cases however the effect on the enzyme is prevailing probably due to individual factors.

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References

  1. Molhuysen J.A., Gerbandy J., De Vries L.A., De Jong J.C., Lenetra J.B., Turner K.P., Borst J.C.G. A licorice extract with desoxycorticosterone like action. Lancet 1: 381, 1950.

    Article  Google Scholar 

  2. Ulmann A., Menard J., Corvol P. Binding of glycyrrhetinic acid to kidney mineralocorticoid and glucocorticoid receptors. Endocrinology 97: 46, 1975.

    Article  CAS  PubMed  Google Scholar 

  3. Armanini D., Karbowiak I., Funder J.W. Affinity of licorice derivatives for mineralocorticoid and glucocorticoid receptors. Clin. Endocrinol. (Oxf). 19: 606, 1983.

    Google Scholar 

  4. Armanini D., Karbowiak I., Krozowski Z., Funder J.W., Adam W.R. The mechanism of mineralocorticoid action of carbenoxolone. Endocrinology 111: 1683, 1982.

    Article  CAS  PubMed  Google Scholar 

  5. Armanini D., Wehling M., Weber P.C. Mineralocorticoid effector mechanism of licorice derivatives in human mononuclear leukocytes. J. Endocrinol. Invest. 12: 303, 1989.

    CAS  PubMed  Google Scholar 

  6. Aterden L.M. Studies with glycyrrhetinic acid. Inhibition on metabolism of steroids in vitro. Biochem. J. 9: 75, 1958.

    Google Scholar 

  7. Tamura Y., Nishikawa T., Yamada K., Yamamoto M., Kumagai A. Effect of glycyrrhetinic acid and its derivatives on 4-Sulpha and 5 μ reductase in rat liver. Arzneimittelforschung 229: 47, 1979.

    Google Scholar 

  8. Latif S.A., Conca T.J., Morris D.J. The effect of the licorice derivative glycyrrhetinic acid,on hepatic 3 α- and 3 β-hydroxysteroid dehydrogenase and 5 α and 5 β-reductase pathways of metabolism of aldosterone in male rats Steroids 55: 52, 1990.

    CAS  Google Scholar 

  9. Stewart P.M., Wallace A.M., Valentino R., Burt D., Shackleton C.H., Edward C.R.W. Mineralocorticoid activity of licorice 11β hydroxysteroid dehydrogenase deficiency comes of age. Lancet 1: 82, 1987.

    Google Scholar 

  10. Farese R.W., Biglieri E.G., Shackleton C.H.L, Irony I., Gomez-Fontes R. Licorice-induced hypermineralocorticism. N. Engl. J. Med. 325: 1223, 1991.

    Article  PubMed  Google Scholar 

  11. Funder J.W., Pearce P.T., Smith R., Smith A. Mineralocorticoid action: target tissue specificity is enzyme, not receptor mediated. Science 242: 583, 1988.

    Article  CAS  PubMed  Google Scholar 

  12. Edwards C.R.W., Stewart P.M., Burt D., Brett L., McIntyre L., Sutanto W.S., de Kloet E.R., Monder C. Localization of 11β hydroxysteroid dehydrogenasetissue specific protector of the mineralocorticoid receptors. Lancet 2: 986, 1988.

    Article  CAS  PubMed  Google Scholar 

  13. Wilson R.C., Harbison M.D., Krozowski Z.S., Funder J.W., Shackleton C.H., Hanauske-Abel H.M., Wei J.Q., Hertecan J., Moran A., Neiberger R.E., Balfe J.W., Fattah A., Daneman D., Licholai T., New M. Several homozigous mutations in the gene for 11β-hydroxysteroid dehydrogenase type 2 in patients with apparent mineralocorticoid excess. J. Clin. Endocrinol. Metab. 80: 3145, 1995.

    CAS  PubMed  Google Scholar 

  14. Bernardi M., D’Intino P., Trevisani F., Cantelli-Forti G.I., Raggi M.A., Turchetto E., Gasbarrini G. Effects of prolonged ingestion of graded doses of licorice by healthy volunteers. Life Science 55: 863, 1994.

    Article  CAS  Google Scholar 

  15. Lan N.C., Matulich D.T., Stockigt J.R., Biglieri E.G., New M., Winter J.S.D., McKenzie J.K., Baxter J.D. Radioreceptor assay of plasma mineralocorticoid activity. Circ. Res. 46(suppl 1): 94, 1976.

    Google Scholar 

  16. Armanini D., Strasser T., Weber P.C. Characterization of aldosterone binding sites in human mononuclear leukocytes. Am. J. Physiol. 248: E388, 1985.

    CAS  PubMed  Google Scholar 

  17. Ventura P., Visconti M., Pifferi G. A simple GLC. Analysis of ammonium glycyrrhizinate. Bollettino Chimico Farmaceutico 117: 211, 1978.

    Google Scholar 

  18. De Groot G., Koops R., Hogendorn E.A., Goewie C.E., Savelkoul T.J., Van Vloten P. Improvement of selectivity and sensitivity by column switching in the determination of glycyrrhizin and glycyrrhetinic acid in human plasma by high performance liquid chromatography. J. Chromatog. 456: 71, 1988.

    Article  Google Scholar 

  19. Monder C., Shackleton C.H.L., Bradlow L., New M., Stoner E., Iohan F., Lakshmi V. The syndrome of apparent mineralocorticoid excess: its association with 11-β-hydroxysteroid-dehydrogenase and 5-β-reductase deficiency and some consequence for corticosteroid metabolism. J. Clin. Endocrinol. Metab. 63: 550, 1986.

    Article  CAS  PubMed  Google Scholar 

  20. Soro A., Ingram M.C., Tonolo G., Glorioso N., Fraser R. Evidence of coexisting changes in 11 hydroxysteroid dehydrogenase and 5-β-reductase activity in subjects with untreated essential hypertension. Hypertension 25: 67, 1995.

    Article  CAS  PubMed  Google Scholar 

  21. Armanini D., Witzgall H., Wehlig M., Kuhnle U., Weber P.C. Aldosterone receptors in different types of primary hyperaldosteronism. J. Clin. Endocrinol. Metab. 5: 101, 1987.

    Article  Google Scholar 

  22. Armanini D., Zennaro M.C., Martella L., Pratesi C., Scali M., Zampollo V. Regulation of aldosterone receptors in hypertension. Steroids 58: 611, 1993.

    Article  CAS  PubMed  Google Scholar 

  23. Monder C., Shackleton C.H.L. 11-β-hydroxysteroid-dehydrogenase fact or fancy? Steroids 44: 383, 1986.

    Article  Google Scholar 

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Authors and Affiliations

  1. Istituto di Semeiotica Medica, University of Padova, via Ospedale 105, 35128, Padova, Italy

    D. Armanini Prof. Dr., C. Pratesi, M. Scali, M. C. Zennaro, S. Zovato, C. Gottardo, M. Simoncini, A. Spigariol & V. Zampollo

  2. Pharmakologisches Institut, University of Heidelberg, Heidelberg, Germany

    S. Lewicka

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  1. D. Armanini Prof. Dr.
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  2. S. Lewicka
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  3. C. Pratesi
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  4. M. Scali
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  5. M. C. Zennaro
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  6. S. Zovato
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  7. C. Gottardo
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  8. M. Simoncini
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  9. A. Spigariol
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  10. V. Zampollo
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Armanini, D., Lewicka, S., Pratesi, C. et al. Further studies on the mechanism of the mineralocorticoid action of licorice in humans. J Endocrinol Invest 19, 624–629 (1996). https://doi.org/10.1007/BF03349029

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  • DOI: https://doi.org/10.1007/BF03349029

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