How does aldosterone act on intercalating β cells? : Journal of the American Society of Nephrology (2023)

Aldosterone is a steroid hormone produced by cells in the zona glomerulosa of the adrenal gland, which serves both K.+and volume homeostasis. An important physiological function is to protect our potassium homeostasis, and aldosterone is released in response to elevated plasma potassium levels. Aldosterone strongly increases renal K+Secretion via upregulation of K-supporting molecular players+It is mainly secreted in the collecting duct (CD). One of the major players in this is the epithelial sodium channel (ENaC), where increased expression of a functional channel at the apical membrane will provide the necessary depolarization to support K persistence.+secretionapproveextrarenal medullary potassium+.a K+Concomitant with the release of aldosterone, exercise also reduces available Na+reabsorptionapproveThe NaCl cotransporter in the distal convoluted tubule, hence Na+Reuptake effectively shifts to more distant CDs, allowing K+secretion. In hypovolemic states where the renin-angiotensin-aldosterone system is activated, aldosterone plays another important role by stimulating ENaC function to prevent Na loss.+in the urine, which can occur. The central role of aldosterone in the regulation of fluid and electrolyte homeostasis is clearly demonstrated in states of hyperhormonal hyperconcentration.For examplein aldosterone-producing adenomas). In aldosterone-producing adenomas, increased urinary potassium becomes visible as a marker of K+depletion and hypokalemia, while increased ENaC function leads to volume expansion leading to hypertension. Aldosterone causes most of its effects.approveThe cytoplasmic mineralocorticoid receptor (MR) dissociates from chaperone heat shock protein 90 by binding to steroid molecules, enters the nucleus, and acts as a transcription factor to alter cellular expression of key proteins. In DC and connecting tubules, MR is present in chief cells, where the role of aldosterone has been extensively studied in recent decades. sodium absorption+Parallel to Cl absorption in CDapproveSLC26A4 transport pendrin a CDb- intercalated cellsb-integrated circuit).1As previously recorded, Na+It limits the upregulation of pendrin, possibly mediated by aldosterone.2,3It was also shown that ClThe absorption in CD depends mainly on the presence of pendrin.1The molecular mechanisms underlying the upregulation of pendrin by elevated aldosterone are unclear. Intercalating (IC) cells express MR, so aldosterone may directly mediate its effectsapproveIC-MR.4means aldosteroneapproveMR regulation depends on the Na of ENaC+Transported in chief cells by pendrin-dependent Clsurrounding transportb-I see. in this issueMasamori, fansale.5Whether this is the case has been addressed. The authors successfully generated IC-specific knockout mice for MR. They clearly demonstrate that loss of MR in the IC significantly reduces function and expression of the pendrin protein. This correlates with lower CD ClTherefore, uptake clearly defines the role of IC-MR as a modulator of CD Cl.absorb. But the problem persists with MR in ICStraightMainly activated by aldosterone or glucocorticoids. The specificity of aldosterone signaling is compromised by glucocorticoids, whose plasma concentrations are approx. 100 times greater. Mineralocorticoids and glucocorticoids bind with approximately the same affinity in MR.6Therefore, an efficient glucocorticoid clearance system (type 2 11β-hydroxysteroid dehydrogenase [11-b-HSD2] enzyme) for many MR expression systems.6In IC, this glucocorticoid disposal system is hypofunctional (if present), so MRI should always be active in principle.4,7Due to the appearance of elevated levels of glucocorticoids. Therefore, glucocorticoids may be nutritional or permissive factors for pendrin function in ICs. Alternatively, a paradigm to maintain aldosterone specificityapprove11-b-HSD2 compensation system may not be suitable for IC-MR. This idea is not far-fetched, since IC expresses a cell-specific variant of MR with a regulatory phosphorylation site at position 843 near the steroid hormone-binding moiety.8Phosphorylation of S843 prevents aldosterone binding to MR and dephosphorylation of S843 is required for aldosterone binding.8It is not clear if this IC-specific element would increase the selectivity of MR in such a way that 11-b- Redundant HSD2 function. This will be an extremely relevant question for future work. In his last job, Phamsale.5also reported the intriguing finding that IC-specific MR deletion triggers long-term effects on ENaC function in CD principal cells. They found that the overall function of ENaC was significantly reduced in this mouse model. The mechanistic understanding of this observation is currently inconclusive. Interestingly, these data are supported by similar effects observed in pendrin knockout mice, also suggesting a reduced function of ENaC in CD.9These observations have led to the hypothesis that the entireb-IC is a prerequisite for the full functionality of the adjacent main battery. Since these cells are not galvanically coupled, the IC on the DC and the main battery can use a local communication system to support normal operation of neighboring cells.1,10In conclusion, our understanding of NaCl management and regulation in CD is steadily advancing towards a more comprehensive model.1The role of Pendrin as Cl uptakeThe transporters in CD are becoming increasingly clear and may ultimately provide alternative targets for pharmacological intervention to increase renal Clexcretion.



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See the related article, "Aldosterone regulates epithelial sodium channel and pendrin activity through largely intercalated cell mineralocorticoid receptor-dependent and independent mechanisms in serum kalio," p. 4.


1. Wall SM: the role of Pendrin in the regulation of blood pressure. Am J Physiol Renal Physiol 310: F193–F203, 2016

(Video) Aldosterone and Renin

2. Verlander JW, Hassell KA, Royaux IE, Glapion DM, Wang ME, Everett LA, et al.: Deoxycorticosterone upregulates PDS (Slc26a4) and musenyre: role of pendrins in mineralocorticoid-induced hypertension. Hypertension 42:356–362,2003

3. Wall SM, Kim YH, Stanley L, Glapion DM, Everett LA, Green ED, et al: NaCl restriction increases renal Slc26a4 through subcellular redistribution: role in Cl protection. Hypertension 44:982- 987, 2004

4. Náray-Fejes-Tóth A, Rusvai E, Fejes-Tóth G: Receptor de mineralocorticoides y 11 beta-esteroides dehydrogenasa actividad i renale hovedceller og indlejrede celler. Soy J Physiol 266: F76-F80, 1994

(Video) Mineralocorticoid Receptor Antagonism in Proteinuric Kidney Disease with Dr. J. Matt Luther

5. Pham T, Verlander J, Wang Y, Romero C, Yue Q, Chen C, et al: Aldosterone regulates pendrin and ENaC through a wide range of serum K+ intercellular mineralocorticoid receptor-dependent and independent mechanisms . J Am Soc Nephrol 31: 483-499, 2020

6. Gomez-Sanchez E, Gomez-Sanchez CE: Den mangefacetterede mineralocorticoid-receptor. Shop Physiol 4:965–994, 2014

(Video) Excretory System and the Nephron

7. Chen L, Lee JW, Chou CL, Nair AV, Battistone MA, Păunescu TG, et al.: Transcriptomes of major mouse renal collecting duct cell types identified by single-cell RNA-seq. Proc Natl Acad Sci U S A 114: E9989–E9998, 2017

8. Shibata S, Rinehart J, Zhang J, Moeckel G, Castañeda-Bueno M, Stiegler AL, et al.: Mineralocorticoid receptor phosphorylation regulates ligand binding and the renal response to hypovolemia and hyperkalemia. Cellular Metabolism 18: 660-671, 2013

(Video) Vascular Tubular Crosstalk in the Renin Angiotensin System

9. Pech V, Wall SM, Nanami M, Bao HF, Kim YH, Lazo-Fernandez Y, et al.: Pendrin gene ablation alters ENaC subcellular distribution and open probability. Am J Physiol Renal Physiol 309: F154–F163, 2015

10. Vallon V, Unwin R, Inscho EW, Leipziger J, Kishore BK: Extracellular nucleotides and P2 receptors in kidney function. Physiological Ap. 100:211-269


collection channel;epithelial sodium transport;ion transport

(Video) Alison Woodworth and Joesph Wiencek - Advances in the Diagnosis of Primary Aldosteronism
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What is the action of aldosterone on intercalated cells? ›

Aldosterone causes sodium to be absorbed and potassium to be excreted into the lumen by principal cells. In alpha intercalated cells, located in the late distal tubule and collecting duct, hydrogen ions and potassium ions are exchanged. Hydrogen is excreted into the lumen, and the potassium is absorbed.

What does aldosterone do to kidney cells? ›

Aldosterone is well known to increase sodium reabsorption and potassium secretion by the kidney. It exerts its main effects on sodium and potassium balance by binding to the mineralocorticoid receptor (MCR) located in the distal convoluted tubule, connecting segment and cortical collecting duct in the kidney.

What are the actions of aldosterone? ›

Aldosterone causes an increase in salt and water reabsorption into the bloodstream from the kidney thereby increasing the blood volume, restoring salt levels and blood pressure.

What are three functions of the hormone aldosterone? ›

Aldosterone regulates the salt and water balance of the body by increasing the retention of sodium and water and the excretion of potassium by the kidneys (and to a lesser extent by the skin and intestines). It also has a limited effect on the metabolism of fats, carbohydrates, and proteins.

What cells does aldosterone target? ›

Classical aldosterone target tissues are kidney, colon, sweat and salivary glands.

What is the action of aldosterone on which part of kidney? ›

Aldosterone, a steroid hormone with mineralocorticoid activity, is mainly recognized for its action on sodium reabsorption in the distal nephron of the kidney, which is mediated by the epithelial sodium channel (ENaC).

What is the role and function of aldosterone? ›

A steroid hormone made by the adrenal cortex (the outer layer of the adrenal gland). It helps control the balance of water and salts in the kidney by keeping sodium in and releasing potassium from the body. Too much aldosterone can cause high blood pressure and a build-up of fluid in body tissues.

What is the role of aldosterone and what triggers its release? ›

Aldosterone signals certain organs, like your kidneys and colon, to increase the amount of sodium they send into your bloodstream or the amount of potassium released in your urine (pee). Aldosterone's effect on sodium increase causes your body to retain water in your blood, which increases blood volume.

What is the function of aldosterone in the kidney quizlet? ›

The main function of aldosterone in the kidney is to increase the reabsorption of sodium ions and the excretion of potassium ions. Aldosterone stimulates the activity of sodium-potassium pumps, which transport ions from the tubular fluid into the bloodstream and vice versa.

What does aldosterone act to stimulate? ›

Aldosterone promotes salt and water retention by stimulating sodium transport mediated by the epithelial sodium channel (ENaC) in the distal nephron.

Where does aldosterone work in the body? ›

Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon.

What are the four factors which regulate aldosterone secretion? ›

Four humoral factors have been shown to play important roles in the regulation of aldosterone secretion. These are ACTH, potassium, sodium and angiotensin II.

Which is a true statement regarding aldosterone? ›

So, the correct answer is 'It produces its effects by increasing membrane permeability to potassium'.

What is the cellular response of aldosterone? ›

Aldosterone activates sodium and potassium channels in principal cells of distal tubule and collecting duct, leading to sodium reabsorption and potassium secretion. In parallel, acid equivalents are secreted in the distal nephron.

What is the most important trigger for aldosterone release? ›

The major factors stimulating aldosterone production and release by the zona glomerulosa are angiotensin II and the serum potassium concentration. The juxtaglomerular apparatus is the principal site of regulation of angiotensin II production.

What happens when aldosterone levels are high? ›

High aldosterone levels can cause high blood pressure and low potassium levels. Low potassium levels may cause weakness, tingling, muscle spasms, and periods of temporary paralysis.

What does aldosterone directly regulate the concentration of? ›

Aldosterone is present in relatively minute amounts in plasma (one one-hundredth of the concentration of hydrocortisone), but its great potency indicates that it plays a major role in regulating the amount of sodium and potassium in the body; through its direct effect on the renal tubule it accelerates renal retention ...

What is the primary role of aldosterone quizlet? ›

The primary function of aldosterone is the protection of sodium balance and the regulation of fluid balance by increasing sodium reabsorption from the renal tubules. Aldosterone is a hormone excreted by the adrenal cortex when the sodium level in the extracellular fluid is decreased.

What is the function of aldosterone and cortisol explain? ›

Your adrenal glands release cortisol during times of stress to help your body get an energy boost and better handle an emergency situation. Aldosterone: Aldosterone is a mineralocorticoid hormone that plays a central role in regulating blood pressure and the levels of sodium and potassium (electrolytes) in your blood.

What is the role of aldosterone in water reabsorption? ›

Aldosterone increases sodium transport by binding to the MR, translocating to the nucleus, and increasing the transcription of sodium channels and transporters, thereby indirectly promoting water reabsorption in the renal distal tubule.

What is the most important regulator of aldosterone? ›

The major physiological regulators of aldosterone production from the adrenal zona glomerulosa are potassium and angiotensin II; other acute regulators include adrenocorticotropic hormone (ACTH) and serotonin.

What factor inhibits aldosterone release? ›

Aldosterone secretion may be inhibited by potassium depletion, inhibitors of the renin-angiotensin system, dopamine and atrial natriuretic factor. The latter appears to be an important physiological regulator of aldosterone secretion.

What blocks the effect of aldosterone? ›

Aldosterone antagonists are diuretics or “water pills.” They may also be called aldosterone receptor blockers. Aldosterone antagonists include: Eplerenone (Inspra) Spirinolactone (Aldactone)

Which of the following most accurately describes the actions of aldosterone? ›

Answer and Explanation: secretion in the collecting ducts. The collecting duct is the distal region of the renal tubule that contains receptors cells for the aldosterone hormone. Aldosterone increases the synthesis of sodium-potassium channels in the epithelial layer of the collecting duct which increases...

How do you increase aldosterone? ›

Potassium directly increases aldosterone secretion by the adrenal cortex and aldosterone then lowers serum potassium by stimulating its excretion by the kidney. High dietary potassium intake increases plasma aldosterone and enhances the aldosterone response to a subsequent potassium or angiotensin II infusion (12).

What are the three transport mechanisms stimulated by aldosterone? ›

The reabsorbed sodium ions are transported out of the tubular epithellium into the renal interstitial fluid and from there into the renal capillary circulation. Three primary mechanisms control aldosterone release—the renin-angiotensin system, potassium, and adrenocorticotropic hormone.

What is the role of the intercalated cells? ›

Intercalated cells are epithelial cells traditionally associated with the regulation of acid-base homeostasis in distal segments of the kidney tubule (Figure 1) (1). These cells also participate in potassium and ammonia transport and have a role in the innate immune system.

How does aldosterone work on ENaC? ›

Aldosterone stimulates sodium transport in the renal collecting duct by activating the epithelial sodium channel (ENaC).

What effect does aldosterone have on channels? ›

In the kidney, aldosterone increases the transcription of the basolateral Na+/K+-ATPase [24] and the apical epithelial Na+ channel (ENaC) [25]. Synthesis of channels and pumps were classified as late effects since they were only detected after 20 h of 1 μM aldosterone exposure [26,27].

Does aldosterone shift potassium into cells? ›

Overview of normal K+ homeostasis.

Insulin, catecholamines, and aldosterone all act to shift K+ into the intracellular space through effects that increase the activity of the Na+-K+-ATPase pump.

What are A vs B intercalated cells? ›

Type A intercalated cells secrete protons via an apical H+-ATPase and reabsorb bicarbonate by a band 3-like Cl-/HCO3-exchanger, AE1, located in the basolateral plasma membrane. Type B intercalated cells secrete bicarbonate by an apical Cl-/HCO3- exchanger that is distinct from AE1 and remains to be identified.

What do alpha and beta intercalated cells do? ›

Specialized cells along the collecting duct—α- and β-intercalated cells—carry out acid or base secretion. The α- and β-intercalated cells are functional mirror images of one another. The α-intercalated cell mediates H+ secretion and the β-intercalated cell HCO3- secretion.

What are alpha intercalated cells vs beta intercalated cells? ›

The intercalated cells come in two different varieties: alpha-intercalated cells (which secrete acid) and beta-intercalated cells (which secrete base).

What does aldosterone respond to? ›

Aldosterone stimulates reabsorption of sodium, sustaining blood volume and pressure in the face of salt deprivation or extracellular fluid depletion. The steroid also stimulates excretion of potassium, protecting extracellular fluid from excessive levels of that ion.

What channel does aldosterone stimulate? ›

Aldosterone upregulates epithelial sodium channels (ENaCs) in the collecting duct and the colon, increasing apical membrane permeability for Na+ and thus absorption.

What happens when you inhibit aldosterone? ›

Aldosterone antagonists block the action of aldosterone, which is a hormone your adrenal glands make. By stopping aldosterone, these drugs cause your kidneys to put extra water and salt into your pee. These medicines also keep your body from getting rid of potassium.

What happens if you have too much aldosterone? ›

The excess aldosterone causes the body to retain both salt and water, and this increase in fluid volume raises your blood pressure. Not all people with primary aldosteronism experience low potassium levels, but those who do may notice: Muscle cramps. Muscle weakness.

Why is potassium lost with aldosterone? ›

Generally, when aldosterone increases, serum potassium decreases, because it promotes secretion in the distal tubules.

Does high potassium stimulate aldosterone? ›

Increased potassium intake lowers blood pressure in patients with hypertension, but increased potassium intake also elevates plasma concentrations of the blood pressure‐raising hormone aldosterone.

Why does potassium trigger aldosterone? ›

In contrast, increases of plasma potassium directly stimulate aldosterone secretion. This effect of potassium on aldosterone serves as a protective mechanism against the development of hyperkalemia.


1. The Brigham Renal Board Review, potassium disorders
(Nephron د. عمار مناف مهدي )
2. Primary Aldosteronism: Nephrology Grand Rounds in Ottawa
(Ottawa Nephrology)
3. Chronic Kidney Disease (CKD) | Etiology, Pathophysiology, Clinical Features, Diagnosis, Treatment
(Ninja Nerd)
4. Potassium physiology (homeostasis)
(Mike Birkhead)
5. Grand Rounds 2021.11.17
(University of Miami Department of Medicine)
6. Aldosteronism - BC Renal Province-wide Rounds (Sept 2020)
(BC Renal)


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