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Nephron. Physiology 2014Aldosterone is classically associated with the regulation of salt and potassium homeostasis but has also profound effects on acid-base balance. During acidosis,... (Review)
Review
Aldosterone is classically associated with the regulation of salt and potassium homeostasis but has also profound effects on acid-base balance. During acidosis, circulating aldosterone levels are increased and the hormone acts in concert with angiotensin II and other factors to stimulate renal acid excretion. Pharmacological blockade of aldosterone action as well as inherited or acquired syndromes of impaired aldosterone release or action impair the renal response to acid loading and cause hyperkalemic renal tubular acidosis. The mineralocorticoid receptor (MR) mediating the genomic effects of aldosterone is expressed in all cells of the distal nephron including all subtypes of intercalated cells. In acid-secretory type A intercalated cells, aldosterone stimulates proton secretion into urine, whereas in non-type A intercalated cells, aldosterone increases the activity of the luminal anion exchanger pendrin stimulating bicarbonate secretion and chloride reabsorption. Aldosterone has also stimulatory effects on proton secretion that may be mediated by a non-genomic pathway. In addition, aldosterone indirectly stimulates renal acid excretion by enhancing sodium reabsorption through the epithelial sodium channel ENaC. Increased sodium reabsorption enhances the lumen-negative transepithelial voltage that facilitates proton secretion by neighboring intercalated cells. This indirect coupling of sodium reabsorption and proton secretion is thought to underlie the fludrocortisone-furosemide test for maximal urinary acidification in patients with suspected distal renal tubular acidosis. In patients with CKD, acidosis-induced aldosterone may contribute to progression of kidney disease. In summary, aldosterone is a powerful regulator of renal acid excretion required for normal acid-base balance.
Topics: Acid-Base Equilibrium; Acidosis, Renal Tubular; Aldosterone; Angiotensin II; Bicarbonates; Epithelial Sodium Channels; Humans; Hyperkalemia; Kidney; Mineralocorticoids; Potassium; Receptors, Mineralocorticoid; Sodium
PubMed: 25377117
DOI: 10.1159/000368266 -
Endocrinology and Metabolism Clinics of... Jun 2015Adrenal steroidogenesis is a dynamic process, reliant on de novo synthesis from cholesterol, under the stimulation of ACTH and other regulators. The syntheses of... (Review)
Review
Adrenal steroidogenesis is a dynamic process, reliant on de novo synthesis from cholesterol, under the stimulation of ACTH and other regulators. The syntheses of mineralocorticoids (primarily aldosterone), glucocorticoids (primarily cortisol), and adrenal androgens (primarily dehydroepiandrosterone and its sulfate) occur in separate adrenal cortical zones, each expressing specific enzymes. Congenital adrenal hyperplasia (CAH) encompasses a group of autosomal-recessive enzymatic defects in cortisol biosynthesis. 21-Hydroxylase (21OHD) deficiency accounts for more than 90% of CAH cases and, when milder or nonclassic forms are included, 21OHD is one of the most common genetic diseases.
Topics: Adrenal Cortex Neoplasms; Adrenal Hyperplasia, Congenital; Adrenocortical Adenoma; Aldosterone; Androgens; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Glucocorticoids; Hormone Replacement Therapy; Humans; Hydrocortisone; Mineralocorticoids; Myelolipoma; Risk Factors
PubMed: 26038201
DOI: 10.1016/j.ecl.2015.02.002 -
Hormones and Behavior Mar 2016The controls of thirst and sodium appetite are mediated in part by the hormones aldosterone and angiotensin II (AngII). The present study examined the behavioral and...
The controls of thirst and sodium appetite are mediated in part by the hormones aldosterone and angiotensin II (AngII). The present study examined the behavioral and neural mechanisms of altered effort-value in animals treated with systemic mineralocorticoids, intracerebroventricular AngII, or both. First, rats treated with mineralocorticoid and AngII were tested in the progressive ratio operant task. The willingness to work for sodium versus water depended on hormonal treatment. In particular, rats treated with both mineralocorticoid and AngII preferentially worked for access to sodium versus water compared with rats given only one of these hormones. Second, components of the mesolimbic dopamine pathway were examined for modulation by mineralocorticoids and AngII. Based on cFos immunohistochemistry, AngII treatment activated neurons in the ventral tegmental area and nucleus accumbens, with no enhancement by mineralocorticoid pretreatment. In contrast, Western blot analysis revealed that combined hormone treatment increased levels of phospho-tyrosine hydroxylase in the ventral tegmental area. Thus, mineralocorticoid and AngII treatments differentially engaged the mesolimbic pathway based on tyrosine hydroxylase levels versus cFos activation.
Topics: Angiotensin II; Animals; Dopamine; Infusions, Intraventricular; Limbic System; Male; Mineralocorticoids; Motivation; Neurons; Nucleus Accumbens; Rats; Rats, Sprague-Dawley; Tyrosine 3-Monooxygenase; Ventral Tegmental Area
PubMed: 26730722
DOI: 10.1016/j.yhbeh.2015.12.002 -
Nutrients Nov 2021The relationship between obesity, arterial hypertension, and excessive salt intake has been known for a long time; however, the mechanism of this relationship remains... (Review)
Review
BACKGROUND
The relationship between obesity, arterial hypertension, and excessive salt intake has been known for a long time; however, the mechanism of this relationship remains not clear.
METHODS
The paper presents a current literature review on the relationship between salt consumption and the development of arterial hypertension in children and adolescents with obesity.
RESULTS
In addition to the traditional theory of hypertension development due to the increase in intravascular volume and disturbances of sodium excretion, recent studies indicate the existence of a complex mechanism related to excessive, pathological secretory activity of adipocytes, insulin resistance, and impaired function of the renin-angiotensin-aldosterone axis. That makes obese children and adolescents particularly vulnerable to the development of salt-sensitive arterial hypertension. Studies performed in many countries have shown that children and adolescents consume more sodium than recommended. It is worth noting, however, that the basis for these recommendations was the extrapolation of data from studies conducted on adults. Moreover, more important than sodium intake is the Na/K ratio and water consumption.
CONCLUSION
Regardless of the population-wide recommendations on reducing salt intake in children, specific recommendations for overweight and obese patients should be developed.
Topics: Adolescent; Child; Feeding Behavior; Homeostasis; Humans; Hyperinsulinism; Hypertension; Insulin Resistance; Mineralocorticoids; Pediatric Obesity; Receptors, Mineralocorticoid; Sodium; Sodium Chloride, Dietary
PubMed: 34836287
DOI: 10.3390/nu13114032 -
Translational Psychiatry Apr 2020Major depressive disorder (MDD) is associated with altered mineralocorticoid receptor (MR) and glucocorticoid receptor function, and disturbed glutamatergic signaling.... (Randomized Controlled Trial)
Randomized Controlled Trial
Major depressive disorder (MDD) is associated with altered mineralocorticoid receptor (MR) and glucocorticoid receptor function, and disturbed glutamatergic signaling. Both systems are closely intertwined and likely contribute not only to the pathophysiology of MDD, but also to the increased cardiovascular risk in MDD patients. Less is known about other steroid hormones, such as aldosterone and DHEA-S, and how they affect the glutamatergic system and cardiovascular disease risk in MDD. We examined salivary cortisol, aldosterone, and DHEA-S secretion after stimulation of MR and glutamatergic NMDA receptors in 116 unmedicated depressed patients, and 116 age- and sex-matched healthy controls. Patients (mean age = 34.7 years, SD = ±13.3; 78% women) and controls were randomized to four conditions: (a) control condition (placebo), (b) MR stimulation (0.4 mg fludrocortisone), (c) NMDA stimulation (250 mg D-cycloserine (DCS)), and (d) combined MR/NMDA stimulation (fludrocortisone + DCS). We additionally determined the cardiovascular risk profile in both groups. DCS had no effect on steroid hormone secretion, while cortisol secretion decreased in both fludrocortisone conditions across groups. Independent of condition, MDD patients showed (1) increased cortisol, increased aldosterone, and decreased DHEA-S concentrations, and (2) increased glucose levels and decreased high-density lipoprotein cholesterol levels compared with controls. Depressed patients show profound alterations in several steroid hormone systems that are associated both with MDD pathophysiology and increased cardiovascular risk. Prospective studies should examine whether modulating steroid hormone levels might reduce psychopathology and cardiovascular risk in depressed patients.
Topics: Adult; Cardiovascular Diseases; Depression; Depressive Disorder, Major; Female; Heart Disease Risk Factors; Humans; Hydrocortisone; Male; Mineralocorticoids; Prospective Studies; Receptors, Mineralocorticoid; Receptors, N-Methyl-D-Aspartate; Risk Factors
PubMed: 32313032
DOI: 10.1038/s41398-020-0789-7 -
British Journal of Pharmacology Jul 2022Brain mineralocorticoid receptors (MR) mediate effects of glucocorticoid hormones in stress adaptation, as well as the effects of aldosterone itself in relation to salt...
Brain mineralocorticoid receptors (MR) mediate effects of glucocorticoid hormones in stress adaptation, as well as the effects of aldosterone itself in relation to salt homeostasis. Brain stem MRs respond to aldosterone, whereas forebrain MRs mediate rapid and delayed glucocorticoid effects in conjunction with the glucocorticoid receptor (GR). MR-mediated effects depend on age, gender, genetic variations, and environmental influences. Disturbed MR activity through chronic stress, certain (endocrine) diseases or during glucocorticoid therapy can cause deleterious effects on affective state, cognitive and behavioural function in susceptible individuals. Considering the important role MR plays in cognition and emotional function in health and disease, MR modulation by pharmacological intervention could relieve stress- and endocrine-related symptoms. Here, we discuss recent pharmacological interventions in the clinic and genetic developments in the molecular underpinnings of MR signalling. Further understanding of MR-dependent pathways may help to improve psychiatric symptoms in a diversity of settings. LINKED ARTICLES: This article is part of a themed issue on Emerging Fields for Therapeutic Targeting of the Aldosterone-Mineralocorticoid Receptor Signaling Pathway. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.13/issuetoc.
Topics: Aldosterone; Brain; Cognition; Glucocorticoids; Humans; Receptors, Glucocorticoid; Receptors, Mineralocorticoid; Signal Transduction
PubMed: 35297038
DOI: 10.1111/bph.15835 -
Frontiers in Endocrinology 2022Hypoaldosteronism can be congenital or acquired, isolated or part of primary adrenal insufficiency, and caused by an aldosterone deficit, resistance, or a combination of...
INTRODUCTION
Hypoaldosteronism can be congenital or acquired, isolated or part of primary adrenal insufficiency, and caused by an aldosterone deficit, resistance, or a combination of both. Reduced mineralocorticoid action can induce a decrease in urine K+ and H+ excretion and an increase in urine Na+ excretion, leading to hyperkalemia, and/or hyponatremia, often combined with metabolic acidosis. We aimed to characterize the clinical manifestations of hypoaldosteronism, and their associated factors.
METHODS
Retrospective analysis of 112 episodes of hypoaldosteronism diagnosed in 86 adult patients from 2012-2019 by the Endocrinology and Nutrition Department of a tertiary hospital. The frequency of hyperkalemia, hypovolemic hyponatremia (HH) and metabolic acidosis (MA), and their associated factors were evaluated.
RESULTS
Patients had a median age of 77 [65 - 84], 55.4% were male. 94.6% cases showed hyperkalemia, 54.5% HH, and 60.3% MA. The mean serum K+ of all cases was 5.4 ± 0.5 mmol/L, Na+: 132.1 ± 6.3 mmol/L, HCO3: 22.6 ± 3.3 mmol/L. Hypoaldosteronism was isolated in the majority of cases: only 6/112 (5%) had primary adrenal insufficiency. Hypovolemia was associated with hyponatremia and a more florid clinical presentation. HH was associated with a combined presence of aldosterone-lowering and mineralocorticoid resistance factors. MA was associated with the presence of mineralocorticoid resistance factors.
CONCLUSIONS
Hypoaldosteronism in adult endocrinological clinical practice is primarily isolated, and acquired. It predisposes not only to the development of hyperkalemia and MA, but also to that of HH. Hypoaldosteronism must be considered in the differential diagnosis of HH with urinary sodium wasting.
Topics: Adult; Humans; Male; Female; Hypoaldosteronism; Hyperkalemia; Aldosterone; Hyponatremia; Mineralocorticoids; Addison Disease; Retrospective Studies; Sodium; Acidosis
PubMed: 36303866
DOI: 10.3389/fendo.2022.990148 -
British Medical Journal Mar 1972
Topics: Addison Disease; Adrenal Insufficiency; Adrenocorticotropic Hormone; Aldosterone; Androgens; Glucocorticoids; Humans; Hydrocortisone; Mineralocorticoids
PubMed: 4335574
DOI: 10.1136/bmj.1.5801.679 -
International Journal of Molecular... Nov 2022In this review, we describe previous basic and clinical studies on autonomous aldosterone production. Over the past decades, mineralocorticoid receptor antagonists... (Review)
Review
In this review, we describe previous basic and clinical studies on autonomous aldosterone production. Over the past decades, mineralocorticoid receptor antagonists (MRAs) have been found to concentration-dependently inhibit steroidogenesis in different degrees. However, many studies have proven the suppressive effects of MRAs on the activities of hormone synthase. The probable factors of cytochrome P-450 reduction, both in microsomes and mitochondria, have also been considered: (1) one of the spironolactone metabolite forms had destructive function, except canrenone, (2) 7α-thio-spironolactone was an obligatory intermediate in the spironolactone-induced CYP450 decrease, and (3) the contributing steroids should have 7α-methylthio or 7α-methylsulfone groups. In previous clinical research, spironolactone-body-containing cells showed a type II pattern of enzyme activity (i.e., enhanced 3β-hydroxysteroid dehydrogenase, glucose-6-phosphate, and NADP-isocitrate dehydrogenase activities and weaken succinate dehydrogenase activity), and the subcapsular micronodules composed of spironolactone-body-containing cells also exhibited a type II pattern and excess aldosterone secretion, indicating that the subcapsular micronodules might be the root of aldosterone-producing adenoma. Moreover, combined with the potential impeditive function to aldosterone secretion, a few cases of spontaneous remission of primary aldosteronism, with normal ranges of blood pressure, plasma potassium, plasma renin activity, and aldosterone renin ratio, have been reported after long-term treatment with MRAs.
Topics: Humans; Mineralocorticoid Receptor Antagonists; Aldosterone; Spironolactone; Mineralocorticoids; Hyperaldosteronism; Renin; Remission, Spontaneous
PubMed: 36430298
DOI: 10.3390/ijms232213821 -
American Journal of Hypertension Jul 2023
Topics: Humans; Renin; Mineralocorticoid Receptor Antagonists; Mineralocorticoids; Hypertension; Aldosterone; Hyperaldosteronism
PubMed: 37061828
DOI: 10.1093/ajh/hpad034