Aldosterone binding to G Protein Estrogen Receptor‐GPER
Bibliographic record
Abstract
MR‐independent effects of aldosterone acting through GPER have been appreciated since 2011. However, whether this related to direct aldosterone‐GPER binding has been disputed. Two previous radioligand studies failed to demonstrate direct aldosterone binding to a putative GPER. However, in neither study was it demonstrated that the radioligand used, bound to a physiological receptor. Further, both utilized 3 H estradiol‐ whose low potency for GPER binding would not be expected to allow GPER receptor identification using vacuum filtration methods related to its high off‐rates. Therefore to determine if aldosterone did bind to GPER, we studied its displacement of [ 3 H] 2‐methoxyestradiol binding ([ 3 H]2ME ‐ a higher affinity GPER‐selective agonist) in SF9 cells with heterologous GPER expression mediated by baculovirus. In this model system, following GPER gene transfer, [ 3 H]2ME demonstrated saturable and reversible binding to a high affinity population of receptors with a Kd = 3.4±0.4 nM and Bmax = 645±49 fmol/mg. In the absence of baculovirus GPER gene transduction, no high affinity [ 3 H]2ME binding was demonstrable in SF9 cells. [ 3 H]2ME binding was guanine‐nucleotide sensitive with a 43±8% reduction in high affinity binding in the presence of GppNHp (100μM). High affinity [ 3 H]2ME binding was displaceable by 2ME [with an IC50 comparable to the determined Kd (1.3±0.4 nM)], the GPER agonist G1, the GPER antagonist G15, estradiol (E2) and aldosterone (Aldo) but not by hydrocortisone (HC) with an order of potency of (2ME>Aldo>E2=G1>G15>>HC). In summary, we demonstrate high affinity [ 3 H]2ME binding to GPER with an order of potency for aldosterone vs. estradiol (vs. hydrocortisone) that parallels the order of potency of their functional effects in previously studied models. These data support the hypothesis that aldosterone mediates its GPER‐dependent effects by direct binding to the receptor. Support or Funding Information Heart and Stroke Foundation of Canada This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".