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18-Oxocortisol: A journey.
Celso E Gomez-Sanchez1, Elise P Gomez-Sanchez2
1Research Service, G. V. (Sonny) Montgomery VA Medical Center, Jackson, MS, USA; Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA.
The Journal of Steroid Biochemistry and Molecular Biology
|March 15, 2023
Summary
Researchers discovered 18-oxocortisol, a weak mineralocorticoid, which helps distinguish primary aldosteronism subtypes. Elevated levels indicate aldosterone-producing adenomas and can predict specific gene mutations like KCNJ5.
Area of Science:
- Endocrinology
- Steroid Biochemistry
- Hypertension Research
Background:
- Investigating mineralocorticoids for low renin hypertension cases.
- Isolation of 18-hydroxycortisol from human urine.
- Exploration of steroid precursors for aldosterone synthesis.
Purpose of the Study:
- Discover novel mineralocorticoids.
- Characterize the newly found steroid 18-oxocortisol.
- Determine the clinical utility of 18-oxocortisol measurements in primary aldosteronism.
Main Methods:
- Incubation of bullfrog adrenals with cortisol.
- Structural elucidation of 18-oxocortisol.
- Measurement of 18-oxocortisol levels in patient subtypes.
Main Results:
- Discovery of 18-oxocortisol, a weak mineralocorticoid.
- Identification of its synthesis in the zona glomerulosa with co-expression of CYP11B2 and CYP17A1.
- Significant elevation of 18-oxocortisol in aldosterone-producing adenomas compared to idiopathic bilateral hyperaldosteronism.
- Correlation of higher 18-oxocortisol levels with KCNJ5 mutations in adenomas.
Conclusions:
- 18-Oxocortisol is a clinically valuable biomarker for differentiating primary aldosteronism subtypes.
- Measurement of 18-oxocortisol aids in predicting somatic mutations within aldosterone-producing adenomas.
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