Aldosterone Totally Explained

Everything about Aldosterone totally explained

| Section2 = | Section3 = }} Aldosterone, is a steroid hormone (mineralocorticoid family) produced by the outer-section (zona glomerulosa) of the adrenal cortex in the adrenal gland, and acts on the distal tubules and collecting ducts of the kidney to cause the conservation of sodium, secretion of potassium, increased water retention, and increased blood pressure. The overall effect of aldosterone is to increase reabsorption of ions and water in the kidney.
Its activity is reduced in Addison's disease and increased in Conn syndrome.
It was first isolated by Simpson and Tait in 1953.

Synthesis

The corticosteroids are synthesized from cholesterol within the adrenal cortex. Most steroidogenic reactions are catalysed by enzymes of the cytochrome P450 family. They are located within the mitochondria and require adrenodoxin as a cofactor (except 21-hydroxylase and 17α-hydroxylase). Aldosterone and corticosterone share the first part of their biosynthetic pathway. The last part is either mediated by the aldosterone synthase (for aldosterone) or by the 11β-hydroxylase (for corticosterone). These enzymes are nearly identical (they share 11β-hydroxylation and 18-hydroxylation functions). But aldosterone synthase is also able to perform a 18-oxidation. Moreover, aldosterone synthase is found within the zona glomerulosa at the outer edge of the adrenal cortex; 11β-hydroxylase is found in the zona fasciculata and reticularis.
Note: aldosterone synthase is absent in other sections of the adrenal gland.

Stimulation

Aldosterone synthesis is stimulated by several factors:

by increase in the plasma concentration of Angiotensin III, a metabolite of Angiotensin II.

by increased plasma angiotensin II, ACTH, or potassium levels, which are present in proportion to plasma sodium deficiencies. (The increased potassium level works to regulate aldosterone synthesis by depolarizing the cells in the zona glomerulosa, which opens the voltage-dependent calcium channels.) The level of angiotensin II is regulated by angiotensin I, which is in turn regulated by the hormone renin. Potassium levels are the most sensitive stimulator of aldosterone.

The ACTH stimulation test is sometimes used to stimulate the production of aldosterone along with cortisol to determine if primary or secondary adrenal insufficiency is present.

by plasma acidosis.

by the stretch receptors located in the atria of the heart. If decreased blood pressure is detected, the adrenal gland is stimulated by these stretch receptors to release aldosterone, which increases sodium reabsorption from the urine, sweat and the gut. This causes increased osmolarity in the extracellular fluid which will eventually return blood pressure toward normal. The secretion of aldosterone has a diurnal rhythm.

Function

Aldosterone is the primary of several endogenous members of the class of mineralocorticoids in human. Deoxycorticosterone is another important member of this class. At the late distal tubule & collecting duct, aldosterone has three main actions:

Acting on the nuclear mineralocorticoid receptors (MR) within the principal cells of the distal tubule and the collecting duct of the kidney nephron, it increases the permeability of the apical (luminal) membrane to potassium and sodium and activates the basolateral Na⁺/K⁺ pumps, stimulating ATP hydrolysis leading to phosphorylation of the pump and a conformational change in the pump exposes the Na⁺ ions to the outside. The phosphorylated form of the pump has a low affinity for Na⁺ ions, hence reabsorbing sodium (Na⁺) ions and water into the blood, and secreting potassium (K⁺) ions into the urine. (Chlorine anions are also reabsorbed in conjunction with sodium cations to maintain the system's electrochemical balance.)

Aldosterone stimulates H⁺ secretion by intercalated cells in the collecting duct, regulating plasma bicarbonate (HCO₃⁻) levels and its acid/base balance.

Aldosterone may act on the central nervous system via the posterior pituitary gland to release vasopressin (ADH) which serves to conserve water by direct actions on renal tubular resorption. (reference needed) Aldosterone is responsible for the reabsorption of about 2% of filtered sodium in the kidneys, which is nearly equal to the entire sodium content in human blood under normal GFR (glomerular filtration rate).
Aldosterone, most probably acting through mineralocorticoid receptors, may positively influence neurogenesis in the dentate gyrus.

Location of receptors

Unlike neuroreceptors, classic steroid receptors are intracellularly located. The aldosterone/MR receptor complex binds on the DNA to specific hormone response element, which leads to gene specific transcription.
Some of the transcribed genes are crucial for transepithelial sodium transport, including the three subunits of the epithelial sodium channel, the Na⁺/K⁺ pumps and their regulatory proteins serum and glucocorticoid-induced kinase, and channel-inducing factor respectively.

Control of aldosterone release from the Adrenal Cortex

The role of the renin-angiotensin system:
Angiotensin is involved in regulating aldosterone and is the core regulation. Angiotensin II acts synergistically with potassium, and the potassium feedback is virtually inoperative when no angiotensin II is present. A small portion of the regulation resulting from angiotensin II must take place indirectly from decreased blood flow through the liver due to constriction of capillaries. When the blood flow decreases so does the destruction of aldosterone by liver enzymes.

The role of sympathetic nerves:
The aldosterone production is also affected to one extent or another by nervous control which integrates the inverse of carotid artery pressure, pain, posture, and probably emotion (anxiety, fear, and hostility) (including surgical stress). Anxiety increases aldosterone, which must have evolved because of the time delay involved in migration of aldosterone into the cell nucleus. Thus, there's an advantage to an animal anticipating a future need from interaction with a predator since too high a serum content of potassium has very adverse effects on nervous transmission.

The role of baroreceptors:
Pressure in the carotid artery decreases aldosterone

The role of the juxtaglomerular apparatus:

The plasma concentration of potassium:
The amount of aldosterone secreted is a direct function of the serum potassium as probably determined by sensors in the carotid artery.

The plasma concentration of sodium:
Aldosterone is a function of the inverse of the sodium intake as sensed via osmotic pressure. The slope of the response of aldosterone to serum potassium is almost independent of sodium intake. Aldosterone is much increased at low sodium intakes, but the rate of increase of plasma aldosterone as potassium rises in the serum isn't much lower at high sodium intakes than it's at low. Thus, the potassium is strongly regulated at all sodium intakes by aldosterone when the supply of potassium is adequate, which it usually is in primitive diets.

Miscellaneous regulation:
ACTH, a pituitary peptide, also has some stimulating effect on aldosterone probably by stimulating DOC formation which is a precursor of aldosterone. Aldosterone is increased by blood loss, pregnancy, and possibly by other circumstances such as physical exertion, endotoxin shock, and burns.

Aldosterone feedback:
Feedback by aldosterone concentration itself is of a non morphological character (that is other than changes in the cells' number or structure) and is poor so the electrolyte feedbacks predominate short term.

Additional images

Image:Corticosteroid-biosynthetic-pathway-rat.png|Corticosteroid biosynthetic pathway in rat Image:Steroidogenesis.gif|Steroidogenesis Image:Corticosterone.svg|Corticosterone Further Information

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