The aldosterone, also known as electrocortina, is a steroid hormone (derived from the perhidrofenantreno cyclopentane) synthesized by glomerular portion of the adrenal cortex and that relates to the control of the levels of sodium, potassium and water in the extracellular fluid.
All steroid hormones are synthesized from cholesterol that can be derived from three sources: from the diet (almost 80%), from acetate, or from the stores of cholesterol esters in the tissues that produce these hormones (tissues steroidogens).
Chemical structure of the hormone aldosterone (Source: Wesalius via Wikimedia Commons)
Cholesterol that enters the diet is transported in human blood plasma by means of low-density lipoproteins or LDL (Low-density Lipoprotein) and is introduced into cells by specific endocytosis mechanisms.
Albumin and plasma globulins (blood proteins) act as transporters for steroid hormones. Aldosterone transport occurs by a nonspecific mechanism and approximately 50% of plasma aldosterone is in the free state.
An increase in ACTH or adrenocorticotropin hormone, angiotensin and plasma potassium, a decrease in plasma sodium and atrial natriuretic factor, are some of the factors that stimulate the synthesis and release of aldosterone.
This hormone participates in the induction of sodium reabsorption in the renal collecting duct, increasing its entry through the sodium channels of this duct. Likewise, the renal output and excretion of potassium and H + is promoted.
Normal plasma aldosterone values depend on sodium intake; they vary between 80-250 pmol / L and can reach up to 300-900 mmol / L in patients with diets high in sodium.
Features
The main function of aldosterone is to regulate the levels of Na + and water in the extracellular fluid, as well as to regulate the secretion of K + and H + by the kidneys and to modify the secretion of ions in other tissues such as the salivary glands, the intestinal mucosa and the glands. sweaty.
Aldosterone promotes renal sodium absorption and excretion of potassium and hydrogen ions, as a result sodium is retained and urinary elimination of potassium and hydrogen ions is increased. Water is reabsorbed along with sodium through an osmotic effect.
Representative schematic of the aldosterone feedback mechanism (Source: OpenStax College via Wikimedia Commons)
Because it handles electrolytes, this hormone is also called the adrenal mineralocorticoid hormone. It is the most potent natural mineralocorticoid and is transported in the blood plasma in a free form or in association with some proteins.
The half-life of aldosterone is about 15-20 minutes and the liver is responsible for its rapid elimination by forming a metabolite from aldosterone called tetrahydroxy aldosterone 3-glucuronide, which is then eliminated by the kidney through urine.
Synthesis
The chemical name for aldosterone is 11β, 21-Dihydroxy-3,20-dioxo-4-pregne-18-al. Its synthesis takes place in the cells of the zona glomerulosa or subcapsular of the cortex of the adrenal glands (very important glands located in the upper region of the kidneys).
Aldosterone synthesis begins with the transport of cholesterol from the cell cytosol into the mitochondria.
The first step is the conversion of cholesterol to pregnenolone, which is then converted to progesterone and then to deoxycorticosterone (DOC), to corticosterone, and finally to aldosterone.
The transport of cholesterol into the aqueous cytosol, where it is poorly soluble, occurs by means of a sterol carrier protein known as "sterol carrier protein 2" or SPD-2. This is the protein in charge of transporting cholesterol to the mitochondria.
Another protein called StAR (Steroidogenic Immediate Regulator) allows the entry of cholesterol into the intermembrane space (through the outer membrane of the mitochondria).
Synthesis of aldosterone (Source: Calvero via Wikimedia Commons)
Inside the mitochondria, most of the steroidogenic enzymes are part of the cytochrome P450 oxidase complex.
The conversion of cholesterol to pregnenolone occurs by the cholesterol side chain cleavage enzyme, better known as P450scc. Enzymes of this type cut the cholesterol side chain in the mitochondria, as well as the hydroxylations at the 20α and 22 positions and cleave the bond between carbons 20-22.
The enzymes 3β-HSD (3β-hydroxysteroid dehydrogenase) and Δ5,4isomerase, which are not part of the P450 complex, mediate the transformation of pregnenolone to progesterone by hydroxylation and isomerization, respectively.
This reaction occurs in the endoplasmic reticulum of aldosterone-producing cells in the adrenal cortex.
The enzyme P450c21 is a 21-hydroxylase that converts progesterone to 11-deoxycorticosterone, which is subsequently hydroxylated by 11β-hydroxylase and converted to corticosterone.
The enzyme 18-hydroxylase or aldosterone synthetase transforms, by hydroxylation, corticosterone into 18-hydroxycorticosterone, which, by exchanging the alcohol at position 18 for an aldehyde group, yields aldosterone.
How is secretion induced?
Both the secretion and the function of aldosterone depend on several elements, among which are natriuretic factor or FNA and angiotensin II. FNA is a peptide hormone synthesized by the atrial muscle and secreted by these cells in response to atrial stretch.
Other factors, although less potent, are also related to the secretion of aldosterone and these are: the adrenocorticotropin hormone (ACTH), plasma sodium and potassium.
ACTH or adrenocorticotropin is a hormone produced by the pituitary. Its secretion is stimulated by CRH or corticotropin-releasing hormone, which is a hormone synthesized and released by the hypothalamus and is part of the hypothalamic-pituitary-adrenal cortex axis for the regulation of aldosterone secretion.
The regulatory mechanism of this hypothalamic-pituitary-adrenal cortex axis is a negative feedback mechanism, where the final products of stimulation end up inhibiting the secretion of the different hormones of this axis.
The increase in angiotensin II is due to stimulation of renin secretion by the granule cells of the renal juxtaglomerular apparatus. These cells secrete renin stimulated by various factors such as:
- Decreased renal perfusion pressure
- Changes in the composition of the tubular fluid that bathes the macula densa in the kidney or
- Stimulation of renal sympathetic nerves and other factors
Renin is a proteolytic enzyme that breaks down angiotensinogen and converts it to angiotensin I, which is converted to angiotensin II by angiotensin II converting enzyme. Angiotensin II, as discussed, stimulates aldosterone release.
If sodium intake increases, plasma volume increases and this, in turn, reflexively, decreases renal sympathetic tone, which also decreases renin and angiotensin production. The increase in plasma volume causes an increase in FNA secretion.
Both the decrease in angiotensin II and the increase in FNA produce a decrease in aldosterone secretion, which in turn increases the renal excretion of sodium and water and thus regulates the concentration of this ion in the face of changes in its consumption.
Action mechanisms
The main target organ for aldosterone is the kidney, specifically the collecting tubule and the distal tubule.
In this area, aldosterone enters cells and binds to an intracellular receptor. The aldosterone binding complex and the receptor diffuse into the nucleus and hormonal functions are initiated.
The ability of aldosterone to increase sodium reabsorption is due to several mechanisms. This hormone increases the number of sodium channels at the luminal border of collecting duct cells.
This occurs, on the one hand, because it stimulates the presentation of these channels on the surface of the cells of the distal convoluted tubule and collecting tubule and, on the other hand, because it increases their synthesis.
Aldosterone indirectly stimulates the sodium / potassium pump on the basolateral surface of collecting tubule cells. This pump draws sodium into the interstitial fluid, which facilitates the entry of sodium into the tubular cell by keeping the electrochemical gradient for this ion high.
Likewise, the amount of sodium that is reabsorbed is dependent on the load. The more sodium the fluid entering the collecting tube brings in, the more sodium will be absorbed, because the greater the transepithelial electrochemical potential that pushes sodium will be. This is increased by aldosterone.
Normal values
The normal values of aldosterone in the blood plasma depend on the sodium intake and the body position in which it is measured.
In the lying position (supine position) and reported under the international system (SI), with a high sodium intake (between 100 and up to 200 mEq / day of sodium), the values vary between 80 and 250 pmol / L which, under units conventional, they would be 3 to 9 ng / dL.
´Graphic representation of the dorsal / supine position (Source: BruceBlaus via Wikimedia Commons)
In the lying position (supine position) with low sodium intake (10 mEq / day sodium), normal values are between 300-900 mmol / L (SI) and 12-36 ng / dL in conventional units.
In a standing position and with high sodium intake, the values vary between 100 and 800 mmol / L (SI) and between 4 and 30 ng / dL. In this same position, but with low sodium intake, normal values are between 450 and 3800 mmol / L (SI) or between 17 and 137 ng / dL in conventional units.
However, each laboratory reports normal values according to the measurement method used.
References
- Gardner, DG, Shoback, D., & Greenspan, FS (2007). Greenspan's basic & clinical endocrinology. McGraw-Hill Medical,
- Murray, RK, Granner, DK, Mayes, P., & Rodwell, V. (2009). Harper's illustrated biochemistry. 28 (p. 588). New York: McGraw-Hill.
- Booth, RE, Johnson, JP, & Stockand, JD (2002). Aldosterone. Advances in physiology education, 26 (1), 8-20.
- Connell, JM, & Davies, E. (2005). The new biology of aldosterone. Journal of Endocrinology, 186 (1), 1-20.
- Ganong, WF, & Barrett, KE (2012). Ganong's review of medical physiology. McGraw-Hill Medical.