Mineralocorticoids

Where are they produced and what do they affect?

Mineralocorticoids belong to the group of hydrophobic steroid hormones (corticosteroids). The general scheme of corticosteroid biosynthesis is as follows: cholesterol → pregnenolone → progesterone → corticosteroids.

• Site of synthesis: Zona glomerulosa (zona glomerulosa) of the adrenal cortex. The cortex occupies the bulk of the gland, has a yellowish-brown color, and is covered by a fibrous capsule.
• Main hormone: aldosterone.
• Endogenous precursor of aldosterone: desoxycorticosterone.
• Target organ: Kidneys.
• Mechanism of action: Induction of the synthesis of specific transport proteins in the renal tubules.

Physiological effects:

1. Water-salt balance: Enhancement of reabsorption of $Na^+$ ions from primary urine in exchange for the excretion of $K^+$ and $H^+$.
2. Fluid retention: An increase in blood salt concentration stimulates the release of antidiuretic hormone (ADH), which leads to water retention in the body.
3. Effect on inflammation: During the proliferation stage (cell division) of the inflammatory process, mineralocorticoids activate tissue regeneration (unlike glucocorticoids, which inhibit it at low doses).

How is secretion regulated?

The secretion of the zona glomerulosa is controlled by the renin-angiotensin system (RAS). This cascade includes the following steps:

1. The kidneys release the enzyme renin.
2. Renin cleaves a fragment from angiotensinogen (a blood protein), resulting in the formation of angiotensin I.
3. Angiotensin-converting enzyme (ACE) converts it into angiotensin II.
4. Angiotensin II stimulates aldosterone production.

Adrenocorticotropic hormone (ACTH) is also a regulator of mineralocorticoid secretion.

Secretion parameters and pharmacokinetics

Under normal salt intake, the following parameters are maintained in the body:

• Daily secretion:
• Aldosterone: 100–200 mcg.
• Desoxycorticosterone: 200 mcg.
• Half-life ($t_{1/2}$):
• Aldosterone: 15–20 min (short half-life).
• Desoxycorticosterone: 70 min.
• Transport and excretion: In the blood, hormones bind to plasma proteins. Excretion occurs via the kidneys: 70% of aldosterone is excreted as a conjugate (tetrahydroaldosterone), and 30% in free form or as 3-oxoglucuronide.

Clinical significance and pathologies

• Adrenal insufficiency (Addison's disease): The disease is accompanied by hypotension and muscle wasting.
• Congenital adrenal hyperplasia (CAH): In the salt-wasting form, prescribing and/or adjusting the dose of mineralocorticoids is indicated. In CAH due to 11$\beta$-hydroxylase deficiency, mineralocorticoids are not prescribed. This form accumulates desoxycorticosterone, which exhibits mineralocorticoid activity.
• Adrenocortical carcinoma: Hormonal hypersecretion is observed in 50–60% of cases. The spectrum of secreted hormones includes mineralocorticoids: aldosterone, corticosterone, and desoxycorticosterone.

Main mineralocorticoid drugs: desoxycorticosterone acetate and fludrocortisone (Cortineff).

Class and exam questions

What else to study on this topic

• Glucocorticoids
• Renin-angiotensin system (RAS)
• Congenital adrenal hyperplasia
• Addison's Disease

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