Aldosterone

GS undefined

Overview
Aldosterone is a steroid hormone (mineralocorticoid family) produced by the outer-section (zona glomerulosa) of the adrenal cortex in the adrenal gland to regulate sodium and potassium balance in the blood.

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 17&alpha;-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 11&beta;-hydroxylase (for corticosterone). These enzymes are nearly identical (they share 11&beta;-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; 11&beta;-hydroxylase is found in the zona fasciculata and reticularis.

Note: aldosterone synthase is absent in other sections of the adrenal gland.

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 two main actions:


 * 1) Acting on mineralocorticoid receptors (MR) on principal cells in the distal tubule of the kidney nephron, it increases the permeability of their apical (luminal) membrane to potassium and sodium and activates their 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.)
 * 2) Aldosterone stimulates H+ secretion by intercalated cells in the collecting duct, regulating plasma bicarbonate (HCO3−) levels and its acid/base balance.
 * 3) 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.

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).

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.

Stimulation of synthesis
Aldosterone synthesis is stimulated by several factors:


 * 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.


 * 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.

Control of aldosterone release from the Adrenal Cortex

 * The role of the renin-angiotensin system
 * The role of sympathetic nerves
 * The role of baroreceptors
 * The role of the juxtaglomerular apparatus
 * The plasma concentration of potassium