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18-Oxocortisol: A journey.

Abstract
The search for mineralocorticoids to explain some cases of low renin hypertension with suppressed aldosterone levels led to the isolation of the abundant steroid 18-hydroxycortisol in human urine. 18-Hydroxycortisol proved to be inactive, but because of its similarity to precursors for the synthesis of aldosterone, bullfrog adrenals were incubated with cortisol, resulting in the discovery of 18-oxocortisol which is structurally similar to aldosterone, but with a 17α-hydroxy group like cortisol. 18-Oxocortisol is a weak mineralocorticoid. Its synthesis occurs primarily in the zona glomerulosa where co-expression of the CYP11B2 (aldosterone synthase) and the CYP17A1 (17α-hydroxylase) occurs in a variable number of cells. The clinical value of the measurement of 18-oxocortisol is that it serves to distinguish subtypes of primary aldosteronism. It is significantly elevated in patients with aldosterone-producing adenomas in comparison to those with idiopathic bilateral hyperaldosteronism and helps predict the type of somatic mutation in the aldosterone-producing adenomas, as it is higher in those with KCNJ5 mutations compared to other gene mutations.
AuthorsCelso E Gomez-Sanchez, Elise P Gomez-Sanchez
JournalThe Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 230 Pg. 106291 (06 2023) ISSN: 1879-1220 [Electronic] England
PMID36921907 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural)
CopyrightCopyright © 2023 Elsevier Ltd. All rights reserved.
Chemical References
  • 18-oxocortisol
  • Hydrocortisone
  • Aldosterone
  • Mineralocorticoids
  • Cytochrome P-450 CYP11B2
  • KCNJ5 protein, human
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
Topics
  • Humans
  • Hydrocortisone
  • Aldosterone
  • Hyperaldosteronism (genetics)
  • Mineralocorticoids
  • Cytochrome P-450 CYP11B2 (genetics, metabolism)
  • Adenoma
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels (genetics)

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