They are a group of hormones (the most important being aldosterone ) that regulate the balance of water and electrolytes (ions such as sodium and potassium) in the body.
Mineralocorticoid hormones act on the kidney, specifically on the tubules of the kidney .
This is a group of hormones made by the cortex of the adrenal gland, named for their effects on the concentrations of sodium, chlorine, and potassium in the extracellular fluid.
It is the adrenocortical hormones that are essential for the maintenance of adequate fluid volume in the extracellular and intravascular fluid compartments, normal cardiac output, and adequate blood pressure levels.
Without a sufficient supply of mineralocorticoids, fatal shock can occur from decreased cardiac output very rapidly.
The main mineralocorticoid is aldosterone, which accounts for most of the activities of this group of hormones.
However, there are several other endogenous hormones (including progesterone and deoxycorticosterone) that have a mineralocorticoid function.
Aldosterone is produced in the zona glomerulosa of the cortex of the adrenal gland and its secretion is mainly mediated by angiotensin II, but also by adrenocorticotrophic hormone (ACTH) and local potassium levels.
The primary effects of mineralocorticoids are increasing sodium reabsorption and potassium secretion in the renal tubules.
Side effects are related to water reabsorption, serum sodium and potassium levels, anion reabsorption, and hydrogen ion secretion.
The net result of these activities is maintenance of fluid and electrolyte balance and therefore adequate cardiac output.
Removal of the adrenal glands can lead to death in just a few days due to several key imbalances:
- The potassium concentration in the extracellular fluid becomes dramatically high.
- Urinary sodium excretion is high.
- The sodium concentration in the extracellular fluid decreases significantly.
The volume of extracellular fluid and blood decrease the heart begins to malfunction, cardiac output decreases and shock occurs.
These phenomena are a direct result of the loss of mineralocorticoid activity and can be largely prevented by replacing salts and mineralocorticoids.
Clearly, mineralocorticoids are extremely critical for the maintenance of life.
The effects of mineralocorticoids are mediated by slow genomic mechanisms through nuclear receptors, as well as rapid non-genomic mechanisms through membrane-associated receptors and signaling cascades.
Mineralocorticoids bind to the mineralocorticoid receptor in the cytosol of the cell and can freely cross the lipid bilayer of the cell. This type of receptor is activated by binding to the ligation.
After a hormone binds to the corresponding receptor, the newly formed receptor-ligament complex translocates into the cell nucleus, where it binds to many hormone response elements (HREs) in the promoter region of genes. target in DNA.
The opposite mechanism is called transrepression.
The ligand-free hormone receptor interacts with heat shock proteins and prevents the transcription of specific genes.
Aldosterone and cortisol (a glucosteroid) have a similar affinity for the mineralocorticoid receptor. However, glucocorticoids circulate at approximately 100 times the level of mineralocorticoids.
An enzyme exists in mineralocorticoid target tissues to prevent glucocorticoid overstimulation.
This enzyme, 11-beta hydroxysteroid dehydrogenase type II, catalyzes the deactivation of glucocorticoids to 11-dehydro metabolites.
Licorice is known to be an inhibitor of this enzyme, and chronic consumption can lead to a condition known as pseudohyperaldosteronism.
Aldosterone and mineralocorticoid receptors
The main steroid with mineralocorticoid activity is aldosterone. Cortisol, the major glucocorticoid in non-rodent species, is said to have “weak mineralocorticoid activity,” which is of some importance because cortisol is secreted much more abundantly than aldosterone.
Another way of saying this is that a small fraction of the body’s mineralocorticoid response is due to cortisol rather than aldosterone.
The mineralocorticoid receptor binds both aldosterone and cortisol with the same affinity.
Furthermore, the same DNA sequence serves as a hormonal response element for the activated (steroid-bound) forms of both mineralocorticoid and glucocorticoid receptors.
An obvious question is:
How can aldosterone stimulate specific biological effects in this type of system, particularly when blood cortisol concentrations are approximately 2000 times higher than aldosterone?
A large part of the answer is that, in cells sensitive to aldosterone, cortisol is effectively destroyed, allowing aldosterone to bind to its receptor without competition.
Aldosterone target cells express the enzyme 11-beta-hydroxysteroid dehydrogenase, which has no effect on aldosterone, but converts cortisol to cortisone, which has only a very weak affinity for the mineralocorticoid receptor.
Essentially, this enzyme “protects” the cell from cortisol and allows aldosterone to work properly.
Some tissues (eg, the hippocampus) express abundant mineralocorticoid receptors but not 11-beta HSD; therefore, they do not show responses to aldosterone because aldosterone is not present in sufficient amounts to compete with cortisol.
Physiological effects of mineralocorticoids
Mineralocorticoids play a fundamental role in regulating the concentrations of minerals, particularly sodium and potassium, in extracellular fluids.
As described above, the loss of these hormones quickly leads to life-threatening abnormalities in fluid and electrolyte balance.
The main target of aldosterone is the distal tubule of the kidney, where it stimulates the exchange of sodium and potassium.
Three primary physiological effects of the aldosterone result:
- Increased sodium reabsorption: sodium loss in the urine decreases with aldosterone stimulation.
- Increased water reabsorption: with the consequent expansion of the extracellular fluid volume. This is an osmotic effect directly related to increased sodium reabsorption.
- Increased renal potassium excretion.
Knowing these effects should quickly suggest the mechanism of cellular action of this hormone.
Aldosterone stimulates the transcription of the gene encoding sodium and potassium ATP, leading to an increased number of “sodium pumps” in the basolateral membranes of tubular epithelial cells.
Aldosterone also stimulates the expression of a sodium channel that facilitates the absorption of sodium from the tubular lumen.
Aldosterone has effects on the sweat glands, salivary glands, and colon, which are essentially identical to those seen in the distal tubule of the kidney.
The greatest net effect is again to conserve sodium in the body by stimulating its resorption or, in the case of the colon, absorption from the intestinal lumen.
Water conservation follows sodium conservation.
Control of aldosterone secretion
Control over aldosterone secretion is truly multifactorial and tied to a web of other factors that regulate fluid and electrolyte composition and blood pressure.
Considering the main effects of aldosterone, it is fairly easy to predict the factors that stimulate or suppress aldosterone secretion.
The two most important regulators of aldosterone secretion are:
- Potassium ion concentration in extracellular fluid: small increases in blood potassium levels strongly stimulate aldosterone secretion.
- Angiotensin II: Activation of the renin-angiotensin system as a result of decreased renal blood flow resulting in the release of angiotensin II, which stimulates aldosterone secretion.
Other factors that stimulate aldosterone secretion include adrenocorticotropic hormone (short-term stimulation only) and sodium deficiency.
Factors that suppress aldosterone secretion include the natural hormone in the atrium, high sodium levels, and potassium deficiency.
An aldosterone deficiency can occur on its own or, more commonly, in conjunction with a glucocorticoid deficiency, and is known as hypoadrenocorticism or Addison’s disease.
Excess aldosterone is seen more frequently in two conditions: increased plasma potassium ( hyperkalemia ) and low vascular volume.
This should make sense considering that plasma potassium and angiotensin II are the main factors that regulate aldosterone secretion, as described above.
Importantly, it is now recognized that approximately 1 in 10 cases of primary hypertension in humans is associated with hyperaldosteronism, most commonly due to aldosterone-secreting adrenal tumors or potassium channel mutations.
Hypertension with hypokalemia and suppression of plasma renin activity is known as mineralocorticoid hypertension.
Although mineralocorticoid hypertension accounts for a small number of patients labeled “essential” hypertensive, it is a potentially reversible cause of high blood pressure.
The most common cause of mineralocorticoid hypertension is probably primary aldosteronism.
Controlled posture studies to measure plasma renin activity and aldosterone concentrations, followed by adrenal imaging, will ensure the differential diagnosis between an aldosterone-producing adenoma and idiopathic adrenal hyperplasia in most cases.
Three monogenic forms of mineralocorticoid hypertension have been described:
- Glucocorticoid-suppressive hyperaldosteronism.
- Liddle’s syndrome.
- The apparent excess of mineralocorticoids.
It is now known that many patients with mineralocorticoid hypertension have normal serum potassium levels.
Until the true prevalence of primary aldosteronism and monogenic forms of mineralocorticoid hypertension is defined, a high index of suspicion is needed in every hypertensive patient.
Hypertensive patients with hypokalemia, along with those with severe hypertension or a family history of hypertension or stroke, should be screened for mineralocorticoid excess.