19-Nor-deoxycorticosterone: A potent mineralocorticoid isolated from the urine of rats with regenerating adrenals

C. E. Gomez-Sanchez, O. B. Holland, B. A. Murry, H. A. Lloyd, L. Milewich

Research output: Contribution to journalArticle

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Abstract

Adrenal regeneration hypertension (ARH) is an experimental form of low renin hypertension in the rat in which an unknown mineralocorticoid(s) appears to contribute to the pathophysiology of the hypertension. To isolate unknown mineralocorticoids, urine of castrated rats with regenerating adrenals was lowered to pH 1.0 with sulfuric acid, incubated for 24-h at room temperature, extracted with ethyl acetate, and subjected to several successive chromatographic purifications. Unknown urinary mineralocorticoid activity was identified and monitored with an aldosterone radioreceptor assay to enable isolation of approximately 1 mg of a pure unknown steroid. Direct probe mass spectrometry, gas chromatography-mass spectrometry, and nuclear magnetic resonance revealed the following characteristics of the isolated steroid: 1) a molecular weight of 316; 2) a deficit in 14 atomic mass units in comparison to deoxycorticosterone (DOC); 21-hydroxy-4-pregnene-3,20-dione) and to the corresponding dimethoxime and dimethoxime-trimethylsilyl derivatives of the unknown steroid and of DOC; and (3) nuclear magnetic resonance spectrum identical to that of DOC except for the absence of the angular C-10 methyl signal. Further characterization revealed circular dichroism of the unknown steroid almost identical to that of DOC; UV absorption maximum at 239 nm, suggesting a 4-en-3-oxo function; and positive blue tetrazolium reaction, indicating a α-ketol. These data suggested that the steroid was 19-nor-DOC. Mass spectrometry of the isolated steroid, authentic 19-nor-DOC, and their dimethoxime-trimethylsilyl derivatives substantiated this conclusion. This is the first reported identification of 19-nor-DOC as a naturally occurring steroid. However, previous bioassay data have established the mineralocorticoid potency of 19-nor-DOC to be 1.5-5.1 times that of DOC. The role of this newly isolated mineralocorticoid in adrenal regeneration hypertension and human hypertenstion remains to be elucidated.

Original languageEnglish (US)
Pages (from-to)708-711
Number of pages4
JournalEndocrinology
Volume105
Issue number3
StatePublished - 1979

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Desoxycorticosterone
Mineralocorticoids
Urine
Steroids
Hypertension
Gas Chromatography-Mass Spectrometry
Regeneration
Magnetic Resonance Spectroscopy
Radioligand Assay
Circular Dichroism
Aldosterone
Renin
Biological Assay
Mass Spectrometry
Molecular Weight

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Gomez-Sanchez, C. E., Holland, O. B., Murry, B. A., Lloyd, H. A., & Milewich, L. (1979). 19-Nor-deoxycorticosterone: A potent mineralocorticoid isolated from the urine of rats with regenerating adrenals. Endocrinology, 105(3), 708-711.

19-Nor-deoxycorticosterone : A potent mineralocorticoid isolated from the urine of rats with regenerating adrenals. / Gomez-Sanchez, C. E.; Holland, O. B.; Murry, B. A.; Lloyd, H. A.; Milewich, L.

In: Endocrinology, Vol. 105, No. 3, 1979, p. 708-711.

Research output: Contribution to journalArticle

Gomez-Sanchez, CE, Holland, OB, Murry, BA, Lloyd, HA & Milewich, L 1979, '19-Nor-deoxycorticosterone: A potent mineralocorticoid isolated from the urine of rats with regenerating adrenals', Endocrinology, vol. 105, no. 3, pp. 708-711.
Gomez-Sanchez CE, Holland OB, Murry BA, Lloyd HA, Milewich L. 19-Nor-deoxycorticosterone: A potent mineralocorticoid isolated from the urine of rats with regenerating adrenals. Endocrinology. 1979;105(3):708-711.
Gomez-Sanchez, C. E. ; Holland, O. B. ; Murry, B. A. ; Lloyd, H. A. ; Milewich, L. / 19-Nor-deoxycorticosterone : A potent mineralocorticoid isolated from the urine of rats with regenerating adrenals. In: Endocrinology. 1979 ; Vol. 105, No. 3. pp. 708-711.
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