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Adrenal Cortex Hormones and ACTH

*Glandula suprarenalis*, *ACTH*

For medical students3 min readUpdated 2026-10-10

Adrenocorticotropic hormone (ACTH) and the hormones of the adrenal cortex form a unified regulatory axis within the body. Their function follows a strict hierarchy: from signals generated by the nervous system to the hypothalamus, the pituitary gland, and finally to the target glands that control key vital processes.

Secretion peakACTH levels reach their maximum right before waking up.
PrecursorAll adrenal cortex hormones are synthesized from cholesterol.
MorphologyThe adrenal cortex is functionally divided into the zona glomerulosa, zona fasciculata, and zona reticularis.
ACTH targetThe primary target of ACTH is the zona fasciculata, which produces glucocorticoids.

Role of the Hypothalamus and Corticotropin-Releasing Hormone

The central link triggering the cascade of reactions in the hypothalamic-pituitary-adrenal axis is corticotropin-releasing hormone (CRH). This regulator is produced in specialized neurosecretory cells of the hypothalamus. The signal for their activation originates from central nervous system structures, with the limbic system playing a leading role.

Upon reaching the anterior pituitary gland (adenohypophysis), CRH acts on specific cells to stimulate the production of a large precursor protein: pro-opiomelanocortin (POMC). This complex molecule subsequently undergoes enzymatic cleavage to yield several biologically active substances simultaneously:

The functions of CRH are not limited to the pituitary gland. In the central nervous system, it acts as a neurotransmitter and neuromodulator. Furthermore, this hormone is actively involved in the central regulation of autonomic functions, notably activating the sympathetic nervous system.

Adrenocorticotropic Hormone (ACTH): Secretion and Mechanisms

ACTH secretion exhibits a well-defined circadian (diurnal) rhythm. Hormone release begins to increase shortly after falling asleep, and its blood concentration reaches peak maximum values immediately before waking.

Regulation of ACTH Levels: The production of this hormone is influenced by a complex set of stimulatory and inhibitory factors. Stimulators of secretion include:

Inhibitors that suppress ACTH production include somatostatin and cortisol. Cortisol exerts its effect via a classic negative feedback mechanism: an increase in its concentration inhibits the synthesis and subsequent secretion of ACTH by the pituitary gland.

Mechanism of Action and Effects: ACTH binds to membrane receptors on the surface of target cells. These receptors are G protein-coupled, and their activation triggers an intracellular signaling pathway involving the adenylate cyclase system.

Physiological effects of ACTH are divided into two categories:

  1. Adrenal effects: The main action of the hormone is directed at stimulating the cells of the zona fasciculata of the adrenal cortex, leading to a robust increase in the synthesis and secretion of glucocorticoids. To a significantly lesser extent, ACTH can stimulate the zona glomerulosa (increasing mineralocorticoid production) and the zona reticularis (enhancing androgen synthesis).
  2. Extra-adrenal effects: ACTH directly stimulates lipolysis (fat breakdown) and promotes melanin synthesis, which externally manifests as hyperpigmentation of the skin.

Structure and Hormones of the Adrenal Cortex

The adrenal cortex is morphologically and functionally subdivided into three distinct zones. Each of these structural units specializes in producing a strictly defined class of hormones:

  1. Zona glomerulosa: Located most superficially and responsible for the synthesis of mineralocorticoids. The main representative of this group is aldosterone, which regulates water-salt balance.
  2. Zona fasciculata: Occupies the middle and most extensive part of the cortex. This is where glucocorticoids are synthesized, with cortisol playing the key role.
  3. Zona reticularis: Adjoins the adrenal medulla and serves as the site of synthesis for sex hormones—androgens.

Biochemical Features and Reception: Despite the variety of substances produced, all steroidogenic activity of the adrenal cortex is based on a single biochemical precursor. Absolutely all cortical hormones are formed from cholesterol with the participation of specific enzymatic systems that sequentially modify the molecule.

Because adrenal cortex hormones are steroids, they easily cross the cell membranes of target cells. Therefore, all steroid hormones utilize intracellular (nuclear) receptors. Following hormone-target receptor binding inside the cell, transcription of specific genes is activated, triggering the synthesis of new proteins and the realization of physiological effects.

Mnemonic

To remember the zones and their hormones, use the association: "Salt glomerulus, sugar fascicle, sex network" (Zona glomerulosa — mineralocorticoids, Zona fasciculata — glucocorticoids, Zona reticularis — androgens).

Frequently asked questions

What are the main physiological effects of cortisol?

The effects of cortisol as a glucocorticoid are diverse: glucocorticoid receptors are present in almost all cells of the body, so they directly or indirectly regulate nearly all aspects of metabolism and participate in adaptation to chronic stress. Main effects:

  • Carbohydrate metabolism — increases blood glucose levels, stimulates hepatic gluconeogenesis, and inhibits peripheral glucose uptake.
  • Protein and lipid metabolism — enhances protein breakdown in skeletal muscle, connective, bone, and lymphoid tissues; increases lipolysis; combined with insulin, promotes lipogenesis in the upper torso, neck, and face.
  • Mineral metabolism — at high concentrations, interacts with mineralocorticoid receptors, increasing Na⁺ and H₂O reabsorption in the renal tubules and enhancing K⁺ excretion.
  • Blood, immune system, and inflammation — decreases blood eosinophil, basophil, and lymphocyte counts, suppresses cellular immunity and, with prolonged therapeutic administration, humoral immunity; in high doses, acts as an immunosuppressant, provides anti-inflammatory effects, and suppresses inflammation.
  • Nervous and endocrine systems — stimulates the synthesis of catecholamines, primarily epinephrine, in the adrenal medulla; increases the sensitivity of adrenergic receptors to catecholamines; and increases sensory sensitivity and CNS excitability.
What is the mechanism of action of aldosterone?

The mechanism of aldosterone action involves inducing the synthesis of transport proteins in the kidneys (distal convoluted tubules and collecting ducts). The primary molecular mechanism is the stimulation of $Na^+$-$K^+$-ATPase gene expression. This leads to enhanced active reabsorption of sodium ions from the primary urine, coupled with increased renal excretion of potassium ($K^+$), hydrogen ($H^+$), and ammonium ions. Sodium retention increases blood osmolarity, which stimulates antidiuretic hormone (ADH) release and leads to water retention in the body.

How does cortisol affect ACTH levels?

Cortisol regulates ACTH levels via a negative feedback mechanism. When cortisol concentrations in the blood rise, it suppresses the synthesis and secretion of ACTH by the pituitary gland.

What is the common precursor for cortisol and aldosterone?

The common biochemical precursor for all steroid hormones of the adrenal cortex, including cortisol and aldosterone, is cholesterol.

Why does skin pigmentation increase with excess ACTH?

ACTH not only shares a common precursor with melanocyte-stimulating hormone (pro-opiomelanocortin), but it also possesses an extra-adrenal effect: it stimulates melanin synthesis in the skin.

Where are receptors for adrenal cortex hormones located?

Receptors for all steroid hormones are intracellular (nuclear). The hormones cross into the cell and activate target gene transcription.

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