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Cited by 233Hormonal Regulation and HypertensionEstrogen and related hormone effectsAdrenal Hormones and Disorders

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The Roles of Plasma Binding and Receptor Specificity in the Mineralocorticoid Action of Aldosterone1

FUNDER, JOHN W., FELDMAN, DAVID, EDELMAN, ISIDORE S.·1973·Endocrinology
DOI 10.1210/endo-92-4-994
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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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Metadata

Authors
FUNDER, J. W., FELDMAN, D., & EDELMAN, I. S.
Affiliations
University of California, San Francisco (US)
ORCID
Venue
Endocrinology
Publisher
The Endocrine Society
Published
1973-04
Volume
92
Issue
4
Pages
994-1004
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/endo-92-4-994
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 › Endocrinology › 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

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