Mineralocorticoids are hormones that belong to the corticosteroids. The hormones play an important role in regulating blood pressure and sodium/potassium balance.
What are mineralocorticoids?
Mineralocorticoids are steroid hormones made by the adrenal gland. Steroid hormones are steroids with hormonal effects. Steroids belong to the lipid class of substances. Lipids are molecules that have lipophilic groups and are usually insoluble in water. The best known and most important steroid for the human body is cholesterol. All lipoproteins and steroid hormones are built up from cholesterol. Generally speaking, mineralocorticoids belong to the corticosteroids. They are a group of 50 steroid hormones produced in the adrenal cortex (NNR). All corticosteroids have a basic structure made up of the hormone progesterone. Based on their biological action, corticosteroids can be divided into three groups. The main representative of the mineralocorticoids is aldosterone, which is formed in the zona glomerulosa of the adrenal cortex. In their chemical structure, mineralocorticoids are similar to glucocorticoids, which also belong to the corticosteroids. However, mineralocorticoids predominantly affect water and mineral balance rather than energy metabolism.
Function, effects, and roles
The most important mineralocorticoid is aldosterone. It exerts its effect in the connecting tubules and in the collecting tubes of the kidneys. There, the hormone binds to and activates mineralocorticoid receptors (MR). Via activation, aldosterone ensures that increased sodium channels (ENaC) and sodium transporters for Na+- and K+-ATPase are incorporated into the plasma membrane. This allows sodium to be transported across the epithelium more easily. This results in increased reabsorption of water. In addition, there is simultaneously an increased excretion of protons, potassium ions and ammonium ions. Overall, aldosterone thus causes an increase in extracellular volume. The potassium concentration in the blood decreases and the pH value increases. Aldosterone has a 1000 times greater effect on mineral balance than the glucocorticoid cortisol. Aldosterone is regulated by the renin-angiotensin-aldosterone system. When the pressure receptors in the renal vessels measure insufficient blood pressure, the hormone renin is secreted. Several conversions eventually produce angiotensin, which stimulates the release of aldosterone. The increase of potassium concentration in the blood serum, the so-called hyperkalemia, can also activate the synthesis of aldosterone. Furthermore, the synthesis of aldosterone is stimulated by ACTH (adrenocorticotropic hormone). Inhibition of mineralocorticoid biosynthesis occurs by dopamine.
Formation, occurrence, properties, and optimal levels
Mineralocorticoids are formed in the adrenal cortex. The adrenal cortex consists of three layers. Aldosterone and the other mineralocorticoids are produced in the zona glomerulosa, the outermost layer of the adrenal cortex. The starting substance is cholesterol. From this, the hormone pregnenolone is formed via intermediate steps. Pregnenolone is a derivative of pregnane. It is the precursor of the hormone progesterone. At the 21β, 18β and 11β positions, 18-hydroxycorticosterone is formed by hydroxylations to produce aldosterone. Oxidation then takes place, producing aldosterone from the hydroxyl group at the C18 atom. Mineralocorticoids occur in varying concentrations in the human body. The normal value of aldosterone in blood plasma is 20 to 150 ng/l.
Diseases and disorders
In adrenal insufficiency and shock, aldosterone levels may be decreased. Primary adrenal insufficiency is also called Addison’s disease. Addison’s disease results, for example, from autoimmunological processes in which antibodies are directed against the hormone-producing cells of the adrenal gland. The storage disease amyloidosis or an infarction in the context of Waterhouse-Friderichsen syndrome can also cause primary adrenocortical insufficiency. The lack of aldosterone leads to sodium losses via the kidney. This triggers a craving for salty foods in affected individuals. The lack of aldosterone causes the mineral and water balance to become unbalanced. Blood pressure drops sharply, causing patients to suffer from circulatory problems.In the worst case, the circulation fails completely and the affected person loses consciousness. Disease states associated with increased secretion of aldosterone are also referred to as hyperaldosteronism. A distinction can be made between primary and secondary hyperaldosteronism. Primary hyperaldosteronism is known as Conn syndrome. It is caused by autonomic overproduction of aldosterone in the adrenal cortex. In most cases, an adenoma in the NNR is responsible for the overproduction of aldosterone. Typical symptoms of primary hyperaldosteronism are hypertension, potassium deficiency in the blood serum and metabolic alkalosis. Patients suffer from headaches, fatigue, increased thirst and muscle weakness. In many cases, there is also increased protein excretion in the urine and decreased concentrating capacity of the kidney. The volume of urine is increased. Secondary hyperaldosteronism is caused by pathologically increased stimulation of the renin-angiotensin-aldosterone system. Such pathological stimulation may occur in chronic renal diseases associated with impaired renal blood flow. These include conditions such as renal artery stenosis, nephrosclerosis, and chronic glomerulonephritis. Due to restricted renal blood flow, more angiotensin II is reactively produced, resulting in increased secretion of aldosterone as part of the RAAS cascade. Diseases associated with decreased circulating blood volume also activate the RAAS. Thus, liver cirrhosis and heart failure can also lead to secondary hyperaldosteronism. Furthermore, diarrhea, vomiting, and the use of laxatives can lead to electrolyte shifts and thus increased activity of the RAAS. Secondary hyperaldosteronism is also associated with the classic triad of hypertension, hypokalemia, and metabolic alkalosis.
