Receptor binding and biological activity of 18 oxocortisol
Abstract
It has been recently demonstrated that cortisol can be metabolized, producing 18-hydroxycortisol and 18-oxocortisol, following the same pathway by which corticosterone is transformed into 18-hydroxycorticosterone and aldosterone. The influence of a hydroxy group in the 17 alpha position of aldosterone or an aldehyde (actually 11-18 hemiacetal) in the 13-methyl of cortisol on the mineralocorticoid and glucocorticoid activities were studied and compared with the parent steroids. The ability of 18-oxocortisol to complete with [3H]aldosterone for binding to the cytosol receptor of rat renal slices was 8.1% in comparison to unlabeled aldosterone. The addition of a specific glucocorticoid 11 beta, 17 beta-dihydroxy-17 alpha-pregnane-1,4,6- trien-20-yn-21-methyl-3-one decreased this binding to 5.6%. The ability of 18-oxocortisol to compete with [3H]dexamethasone for binding to the renal cytosol receptor was 0.2% that of unlabeled dexamethasone and in the HTC whole cell assay was 1.06% and 3.8% that of unlabeled dexamethasone and cortisol, respectively. The mineralocorticoid activity of 18-oxocortisol in the adrenalectomized rat bioassay was 0.6% that of aldosterone. The glucocorticoid activity in in vitro bioassays was 3.1% compared with that of a cortisol when the induction of tyrosine aminotransferase in HTC cells was measured and 4% when the inhibition of fibroblast L-929 growth was measured. The significance of 18-oxocortisol in the pathogenesis of the hypertension in patients with primary aldosteronism is still unclear.
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18-Hydroxycortisol and 18-oxocortisol are often referred to as 'hybrid steroids' because they require enzymatic machinery from both the glucocorticoid and mineralocorticoid pathways.
“These metabolites are often referred to as “hybrid steroids” as they require enzymatic machinery from both the glucocorticoid and mineralocorticoid pathways [[261], [262], [263]].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [262]
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- Authors
- GOMEZ-SANCHEZ, C. E., GOMEZ-SANCHEZ, E. P., SMITH, J. S., FERRIS, M. W., & FOECKING, M. F.
- Affiliations
- University of South Florida (US)
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1985-01
- Volume
- 116
- Issue
- 1
- Pages
- 6-10
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2035213011
- Cited by
- 44
- References
- 15
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 2 · 2019: 2 · 2017: 1
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (K04-921)
- National Heart, Lung, and Blood Institute (HL27255)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- 18-oxocortisol, cortisol metabolism, mineralocorticoid activity, glucocorticoid activity, mineralocorticoid receptor, 18-hydroxycortisol, aldosterone, primary aldosteronism, hypertension
- MeSH terms
- Adrenalectomy, Aldosterone, Animals, Binding, Competitive, Biological Assay, Cytosol, Dexamethasone, Fibroblasts, Hydrocortisone, Kidney, Male, Potassium, Receptors, Glucocorticoid, Receptors, Steroid, Sodium, Tyrosine Transaminase, Receptors, Mineralocorticoid, Rats
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