The Roles of Plasma Binding and Receptor Specificity in the Mineralocorticoid Action of Aldosterone1
Abstract
The current hypothesis of the mechanism of action of aldosterone includes an initiating step of binding of the steroid to stereospecific receptor proteins in target tissues. In view of the very low circulating levels of aldosterone relative to other adrenal steroids, there must exist potent specificity—conferring mechanisms to insure appropriate aldosterone occupancy of mineralocorticoid receptors. Two specificity—conferring mechanisms are described which are posited to allow aldosterone occupancy of its appropriate receptor.In vitro, renal aldosterone binding sites are shown to fall into two classes. Those with a higher affinity for aldosterone—Kdlss (37 C)≅ 5X10-10—are termed Type I; those with a lower affinity—Kdiss (37 C)≅ 2.5 X lO-8— Type II. Desoxycorticosterone (DOC) has ∼80% the affinity of aldosterone for both sites. Corticosterone (B) has a high affinity for Type II sites, but less than 2% of the affinity of aldosterone for Type I. From the relative affinities of the three steroids for Type I, these sites are postulated to be mineralocorticoid receptors. However, even taking these relative affinities into account, the differences in plasma levels of aldosterone, B, and DOC are such that the mineralocorticoid receptors would be largely, and presumably inappropriately, occupied in vivo by B and DOC. On the basis of a series of in vivo infusion experiments, the second specificity—conferring mechanism, necessary to allow aldosterone occupancy of renal mineralocorticoid receptors, is demonstrated to be the preferential (B > DOC > > aldosterone) plasma binding of the potential competing steroids. The ability of aldosterone to occupy the mineralocorticoid receptors under physiological conditions is therefore a function both of the very low affinity of the Type I receptors for corticosterone, and the extensive, preferential plasma binding of DOC and corticosterone. (Endocrinology92: 994, 1973)
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Corticosteroid-binding globulin binds cortisol with high capacity and affinity, reducing free glucocorticoid levels to about 10%, while aldosterone circulates mainly in free form.
“Corticosteroid-binding globulin binds cortisol with a high capacity and affinity, reducing free GC levels to ~%, whereas aldosterone circulates mainly in its free form ().”
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- Authors
- FUNDER, J. W., FELDMAN, D., & EDELMAN, I. S.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1973-04
- Volume
- 92
- Issue
- 4
- Pages
- 994-1004
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2156614560
- Cited by
- 232
- References
- 0
- Citations by year
- 2024: 1 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 1
- FWCI
- 9.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- 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
- aldosterone, mineralocorticoid receptor, receptor specificity, deoxycorticosterone, corticosterone, receptor occupancy
- MeSH terms
- Aldosterone, Animals, Binding Sites, Binding, Competitive, Corticosterone, Cytosol, Desoxycorticosterone, Kidney, Male, Protein Binding, Tritium, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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