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. 1968 Jun;47(6):1425–1434. doi: 10.1172/JCI105834

Sites of action of sodium depletion on aldosterone biosynthesis in the dog

Warren W Davis 1, Lawrence R Burwell 1, Alfred G T Casper 1, Frederic C Bartter 1
PMCID: PMC297298  PMID: 4297478

Abstract

Secretion of cortisol, corticosterone, and aldosterone was measured in vivo in normal and sodium-depleted hypophysectomized dogs. Biogenesis of steroids was then measured in vitro with outer slices of the adrenals of the same dogs. In some studies, metyrapone or puromycin was added.

In vivo, sodium depletion stimulated the production of cortisol, corticosterone, and aldosterone. In vitro, tissues from sodium-depleted animals released more aldosterone, but less corticosterone than those from sodium-replete controls.

The results are interpreted to indicate that (a) biosynthesis of aldosterone is regulated at at least two sites in the biosynthetic pathway. The final conversion, that of corticosterone to aldosterone, is stimulated by sodium depletion. This effect persists for at least 3 hr while slices from sodium-depleted dogs are incubated in vitro. Stimulation at this site is thus relatively stable in vitro; its activation by sodium depletion is not inhibited by puromycin in the dog. Stimulation at this site can explain, at least in part, the increased effectiveness of adrenocorticotropin (ACTH) on aldosterone biogenesis during sodium depletion.

(b) the earlier site at which sodium depletion stimulates the secretion of aldosterone is “above” the position of desoxycorticosterone in the pathway; it is probably at the conversion of cholesterol to pregnenolone. Stimulation at this site is quickly lost during incubation of adrenal slices. It is thus relatively unstable in vitro; its activation by sodium depletion is inhibited by puromycin in the dog.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BARTTER F. C., DUNCAN L. E., Jr, LIDDLE G. W. Dual mechanism regulating adrenocortical function in man. Am J Med. 1956 Sep;21(3):380–386. doi: 10.1016/0002-9343(56)90038-9. [DOI] [PubMed] [Google Scholar]
  2. BINNION P. F., DAVIS J. O., BROWN T. C., OLICHNEY M. J. MECHANISMS REGULATING ALDOSTERONE SECRETION DURING SODIUM DEPLETION. Am J Physiol. 1965 Apr;208:655–661. doi: 10.1152/ajplegacy.1965.208.4.655. [DOI] [PubMed] [Google Scholar]
  3. BLAIR-WEST J. R., COGHLAN J. P., DENTON D. A., MUNRO J. A., WINTOUR M., WRIGHT R. D. THE EFFECT OF BILATERAL NEPHRECTOMY AND MIDCOLLICULAR DECEREBRATION WITH PINEALECTOMY AND HYPOPHYSECTOMY ON THE CORTICOSTEROID SECRETION OF SODIUM-DEFICIENT SHEEP. J Clin Invest. 1964 Aug;43:1576–1595. doi: 10.1172/JCI105034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bledsoe T., Island D. P., Liddle G. W. Studies of the mechanism through which sodium depletion increases aldosterone biosynthesis in man. J Clin Invest. 1966 Apr;45(4):524–530. doi: 10.1172/JCI105366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Burrow G. N., Mulrow P. J., Bondy P. K. Protein synthesis and aldosterone production. Endocrinology. 1966 Nov;79(5):955–963. doi: 10.1210/endo-79-5-955. [DOI] [PubMed] [Google Scholar]
  6. CARPENTER C. C., DAVIS J. O., AYERS C. R. Relation of renin, angiotensin II, and experimental renal hypertension to aldosterone secretion. J Clin Invest. 1961 Nov;40:2026–2042. doi: 10.1172/JCI104429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DAVIS J. O., AYERS C. R., CARPENTER C. C. Renal origin of an aldosterone-stimulating hormone in dogs with thoracic caval constriction and in sodium-depleted dogs. J Clin Invest. 1961 Aug;40:1466–1474. doi: 10.1172/JCI104377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DAVIS J. O., CARPENTER C. C., AYERS C. R., HOLMAN J. E., BAHN R. C. Evidence for secretion of an aldosterone-stimulating hormone by the kidney. J Clin Invest. 1961 Apr;40:684–696. doi: 10.1172/JCI104301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. DOMINGUEZ O. V., SAMUELS L. T. MECHANISM OF INHIBITION OF ADRENAL STEROID 11BETA-HYDROXYLASE BY METHOPYRAPONE (METOPIRONE). Endocrinology. 1963 Sep;73:304–309. doi: 10.1210/endo-73-3-304. [DOI] [PubMed] [Google Scholar]
  10. Davis W. W., Burwell L. R., Kelley G., Casper A. G., Bartter F. C. Studies of the loci of stimulation of aldosterone biosynthesis during sodium depletion. Biochem Biophys Res Commun. 1966 Jan 24;22(2):218–222. doi: 10.1016/0006-291x(66)90435-9. [DOI] [PubMed] [Google Scholar]
  11. ERTEL R. J., UNGAR F. IN VITRO EFFECT OF 2-METHYL-1,2-BIS(3-PYRIDYL)-1-PROPANONE (SU-4885) AND NADPH IN THE MOUSE ADRENAL. Endocrinology. 1964 Dec;75:949–956. doi: 10.1210/endo-75-6-949. [DOI] [PubMed] [Google Scholar]
  12. Erickson R. E., Ertel R. J., Ungar F. Effect of Su-4885 on steroid 18-hydroxylation in the mouse adrenal in vitro. Endocrinology. 1966 Feb;78(2):343–349. doi: 10.1210/endo-78-2-343. [DOI] [PubMed] [Google Scholar]
  13. FARESE R. V. INHIBITION OF THE STEROIDOGENIC EFFECT OF ACTH AND INCORPORATION OF AMINO ACID INTO RAT ADRENAL PROTEIN IN VITRO BY CHLORAMPHENICOL. Biochim Biophys Acta. 1964 Aug 12;87:699–701. doi: 10.1016/0926-6550(64)90292-0. [DOI] [PubMed] [Google Scholar]
  14. FERGUSON J. J., Jr PROTEIN SYNTHESIS AND ADRENOCORTICOTROPIN RESPONSIVENESS. J Biol Chem. 1963 Aug;238:2754–2759. [PubMed] [Google Scholar]
  15. Garren L. D., Ney R. L., Davis W. W. Studies on the role of protein synthesis in the regulation of corticosterone production by adrenocorticotropic hormone in vivo. Proc Natl Acad Sci U S A. 1965 Jun;53(6):1443–1450. doi: 10.1073/pnas.53.6.1443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. KAHNT F. W., NEHER R. On the specific inhibition of adrenal steroid biosynthesis. Experientia. 1962 Nov 15;18:499–501. doi: 10.1007/BF02151596. [DOI] [PubMed] [Google Scholar]
  17. KAPLAN N. M., BARTER F. C. The effect of ACTH, renin, angiotensin II, and various precursors on biosynthesis of aldosterone by adrenal slices. J Clin Invest. 1962 Apr;41:715–724. doi: 10.1172/JCI104530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. KLIMAN B., PETERSON R. E. Double isotope derivative assay of aldosterone in biological extracts. J Biol Chem. 1960 Jun;235:1639–1648. [PubMed] [Google Scholar]
  19. Kraulis I., Birmingham M. K. Inhibition of the biosynthesis of 18-hydroxy-11-deoxycorticos terone by SU-4885. Can J Biochem. 1965 Sep;43(9):1471–1476. doi: 10.1139/o65-165. [DOI] [PubMed] [Google Scholar]
  20. LAMB J. C., ISAACS J. P., BLOOM W. L., HARMER D. S. ELECTRICAL THROMBOSIS OF BLOOD VESSELS: A VOLTAGE-DEPENDENT PHENOMENON. Am J Physiol. 1965 May;208:1006–1008. doi: 10.1152/ajplegacy.1965.208.5.1006. [DOI] [PubMed] [Google Scholar]
  21. LIDDLE G. W., ISLAND D., LANCE E. M., HARRIS A. P. Alterations of adrenal steroid patterns in man resulting from treatment with a chemical inhibitor of 11 beta-hydroxylation. J Clin Endocrinol Metab. 1958 Aug;18(8):906–912. doi: 10.1210/jcem-18-8-906. [DOI] [PubMed] [Google Scholar]
  22. MARIEB N. J., MULROW P. J. ROLE OF THE RENIN-ANGIOTENSIN SYSTEM IN THE REGULATION OF ALDOSTERONE SECRETION IN THE RAT. Endocrinology. 1965 Apr;76:657–664. doi: 10.1210/endo-76-4-657. [DOI] [PubMed] [Google Scholar]
  23. MULROW P. J., GANONG W. F., CERA G., KULJIAN A. The nature of the aldosterone-stimulating factor in dog kidneys. J Clin Invest. 1962 Mar;41:505–518. doi: 10.1172/JCI104504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. SAFFRAN M., SCHALLY A. V. In vitro bioassay of corticotropin: modification and statistical treatment. Endocrinology. 1955 May;56(5):523–532. doi: 10.1210/endo-56-5-523. [DOI] [PubMed] [Google Scholar]
  25. SIEKEVITZ P. Uptake of radioactive alanine in vitro into the proteins of rat liver fractions. J Biol Chem. 1952 Apr;195(2):549–565. [PubMed] [Google Scholar]
  26. SLATER J. D., BARBOUR B. H., HENDERSON H. H., CASPER A. G., BARTTER F. C. INFLUENCE OF THE PITUITARY AND THE RENIN-ANGIOTENSIN SYSTEM ON THE SECRETION OF ALDOSTERONE, CORTISOL, AND CORTICOSTERONE. J Clin Invest. 1963 Sep;42:1504–1520. doi: 10.1172/JCI104835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. STACHENKO J., GIROUD C. J. FURTHER OBSERVATIONS ON THE FUNCTIONAL ZONATION OF THE ADRENAL CORTEX. Can J Biochem. 1964 Dec;42:1777–1786. doi: 10.1139/o64-188. [DOI] [PubMed] [Google Scholar]

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