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 is the activity of central nervous system structures, among which the limbic system plays a leading role.
Reaching the anterior pituitary gland (adenohypophysis), CRH acts on specific cells and stimulates the production of a large precursor protein — proopiomelanocortin. This complex molecule subsequently undergoes enzymatic cleavage, resulting in the formation of several biologically active substances simultaneously:
- Adrenocorticotropic hormone (ACTH);
- Melanocyte-stimulating hormone;
- $\beta$-endorphin and certain other peptides.
The functions of CRH are not limited to its effect on 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 body functions, specifically causing activation of the sympathetic division of the autonomic nervous system.
Adrenocorticotropic hormone (ACTH): secretion and mechanisms
ACTH secretion has a pronounced diurnal (circadian) rhythm. Hormone release begins to increase shortly after a person falls asleep, and its blood concentration reaches peak, maximum values immediately before awakening.
Regulation of ACTH levels: The production of this hormone is influenced by a complex set of stimulating and inhibitory factors. Stimulators of secretion include:
- CRH (is the primary and most potent activator);
- Antidiuretic hormone (also known as ADH or vasopressin);
- Norepinephrine;
- Angiotensin II.
Inhibitors that suppress ACTH production are somatostatin and cortisol. The action of cortisol is mediated by a classical 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:
- Adrenal effects: the main action of the hormone is aimed at stimulating the cells of the zona fasciculata of the adrenal cortex, which leads to a dramatic enhancement of the synthesis and secretion of glucocorticoids. To a significantly lesser extent, ACTH is able to stimulate the zona glomerulosa (increasing mineralocorticoid production) and the zona reticularis (enhancing androgen synthesis).
- Extra-adrenal effects: ACTH directly stimulates fat breakdown processes (lipolysis) and also promotes increased melanin synthesis, which externally manifests as enhanced skin pigmentation.
Structure and hormones of the adrenal cortex
The adrenal cortex is morphologically and functionally divided into three distinct zones. Each of these structural units specializes in the production of a strictly defined class of hormones:
- 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.
- Zona fasciculata: occupies the middle and most extensive part of the cortex. This is where glucocorticoids are synthesized, with cortisol playing the key role.
- Zona reticularis: lies adjacent to the adrenal medulla and is the site of synthesis of male 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 through the participation of specific enzymatic systems that sequentially modify the molecule.
Since adrenal cortex hormones are steroids, they easily penetrate the cell membranes of target cells. Therefore, all steroid hormones are characterized by intracellular (nuclear) receptors. Upon binding of the hormone to the receptor inside the cell, the transcription processes of specific genes are activated, which triggers the synthesis of new proteins and the realization of the physiological effect.
Briefly: answers to topical 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 almost all components of metabolism and participate in adaptation to chronic stress. Main effects:
- Carbohydrate metabolism — increases blood glucose levels, stimulates gluconeogenesis in the liver, and suppresses glucose utilization by tissues.
- Protein and fat metabolism — enhances protein breakdown in skeletal muscles, connective, bone, and lymphoid tissues, and enhances lipolysis; together with the effects of insulin, it promotes increased lipogenesis in the upper body, neck, and face.
- Mineral metabolism — in high concentrations, it interacts with mineralocorticoid receptors, increases Na⁺ and H₂O reabsorption in the renal tubules, and enhances K⁺ excretion.
- Blood, immune system, and inflammation — decreases the number of eosinophils, basophils, and lymphocytes in the blood, weakens cellular immunity, and with prolonged therapeutic exposure, humoral immunity as well; in high doses, it acts as an immunosuppressant, exerts anti-allergic effects, and inhibits inflammatory processes.
- Nervous and endocrine systems — stimulates the synthesis of catecholamines, primarily adrenaline, 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 action of aldosterone 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, with a simultaneous increase in the renal excretion of potassium ($K^+$), hydrogen ($H^+$), and ammonium ions. Sodium retention increases the salt concentration in the blood, which stimulates the release of antidiuretic hormone (ADH) and leads to water retention in the body.
To remember the zones and their hormones, use the association: "A glomerulus of salt, a fascicle of sugar, a net of sex" (Zona glomerulosa — mineralocorticoids, Zona fasciculata — glucocorticoids, Zona reticularis — androgens).
Class and exam questions
How does cortisol affect ACTH levels?
Cortisol regulates ACTH levels via a negative feedback loop. When cortisol concentration in the blood increases, it inhibits the synthesis and secretion of ACTH by the pituitary gland.
What is the common precursor for cortisol and aldosterone?
The sole biochemical precursor for all steroid hormones of the adrenal cortex, including cortisol and aldosterone, is cholesterol.
Why does skin pigmentation increase with ACTH excess?
ACTH is not only formed from a common precursor with melanocyte-stimulating hormone (pro-opiomelanocortin), but also has an extra-adrenal effect of its own — stimulating melanin synthesis in the skin.
Where are receptors for adrenocortical hormones located?
Receptors for all steroid hormones are intracellular (nuclear). Hormones penetrate inside the cell and activate target gene transcription.
What else to study on this topic
- Mechanisms of the adenylate cyclase system in signal transduction from ACTH
- The process of proteolytic cleavage of pro-opiomelanocortin in the adenohypophysis
- Specific enzymatic systems involved in the conversion of cholesterol into steroids
- The relationship between corticotropin-releasing hormone and the sympathetic division of the autonomic nervous system
Master the entire topic in the "Physiology" course
This is a summary. The course covers everything tested in classes and exams.
- Full study guide on "Adrenal Cortex Hormones and ACTH" and 4,128 more pages of the subject
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 114 video lessons on the subject
Other topics in the section «Hormonal regulation of physiological functions»
Free video lessons: PhysiologyShort lessons with study notes — no registration required.
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.