What is the function of ACTH?


Adrenocorticotropic hormone (ACTH), also known as corticotropin, is a hormone produced by the pituitary gland. It plays a crucial role in the functioning of the adrenal glands and the production of cortisol, a stress hormone. ACTH is a key component of the hypothalamic-pituitary-adrenal (HPA) axis, which is responsible for regulating the body’s response to stress and maintaining homeostasis. In this article, we will explore the function of ACTH in detail, covering various subtopics related to its role.

The Structure of ACTH

ACTH is a peptide hormone composed of 39 amino acids. It belongs to the melanocortin family of peptides and is derived from a larger precursor molecule called pro-opiomelanocortin (POMC). POMC is processed into various biologically active peptides, including ACTH, in response to specific enzymatic cleavage.

ACTH Receptors

ACTH exerts its effects by binding to specific receptors on the surface of target cells. The primary receptor for ACTH is the melanocortin 2 receptor (MC2R), which is predominantly found in the adrenal cortex. MC2R activation triggers a cascade of intracellular signaling events that ultimately leads to the synthesis and secretion of cortisol.

ACTH Synthesis and Secretion

ACTH is synthesized and secreted by specialized cells called corticotrophs in the anterior pituitary gland. Its production is regulated by the hypothalamus through the release of corticotropin-releasing hormone (CRH). CRH stimulates the pituitary gland to produce and release ACTH into the bloodstream.

The secretion of ACTH follows a diurnal rhythm, with the highest levels typically observed in the early morning and the lowest levels at night. This rhythmic pattern is controlled by the hypothalamic circadian clock and is influenced by various factors, including sleep-wake cycles, stress, and hormonal feedback mechanisms.

ACTH and the Adrenal Cortex

ACTH acts on the adrenal cortex, the outer layer of the adrenal glands, to stimulate the production of glucocorticoids, primarily cortisol. It does so by binding to MC2R receptors on the surface of adrenal cortical cells, leading to the activation of enzymes involved in steroidogenesis.

Glucocorticoids, such as cortisol, are essential for maintaining metabolic and immune homeostasis. They regulate a wide range of physiological processes, including glucose metabolism, protein synthesis, inflammation, and stress response. ACTH plays a vital role in the regulation of cortisol production, ensuring its appropriate levels in the body.

Regulation of ACTH Secretion

ACTH secretion is tightly regulated through a negative feedback loop involving cortisol and other factors. When cortisol levels rise, it inhibits the release of CRH and ACTH, reducing further cortisol production. Conversely, low cortisol levels lead to increased CRH and ACTH secretion, promoting cortisol synthesis.

In addition to cortisol, other factors can modulate ACTH secretion. For example, stress, physical activity, and certain medications can stimulate ACTH release. However, the exact mechanisms underlying these regulatory processes are complex and involve interactions between the hypothalamus, pituitary gland, and adrenal glands.


  1. What are the symptoms of ACTH deficiency?

    ACTH deficiency can lead to a condition known as adrenal insufficiency or hypocortisolism. Symptoms may include fatigue, weight loss, low blood pressure, dizziness, salt cravings, and darkening of the skin.

  2. Can ACTH be used as a therapeutic agent?

    Yes, synthetic ACTH, known as cosyntropin or tetracosactide, can be used as a diagnostic tool to assess adrenal gland function or as a treatment for certain conditions, such as primary adrenal insufficiency or infantile spasms.

  3. Is there any relationship between ACTH and melanin production?

    While ACTH and melanin are both derived from the POMC precursor molecule, their regulation and functions are distinct. ACTH primarily acts on the adrenal glands, while melanin production is regulated by melanocyte-stimulating hormone (α-MSH), another peptide derived from POMC.

  4. What happens if there is excessive ACTH production?

    Excessive ACTH production, usually due to a tumor in the pituitary gland or elsewhere, can lead to a condition called Cushing’s disease. Symptoms of Cushing’s disease include weight gain, rounded face, high blood pressure, diabetes, and thinning of the skin.

  5. Can stress affect ACTH levels?

    Yes, stress can stimulate the release of CRH from the hypothalamus, leading to increased ACTH secretion. This, in turn, triggers the production of cortisol, preparing the body for the stress response.

  6. What are the primary functions of cortisol?

    Cortisol plays a crucial role in regulating metabolism, immune response, and stress adaptation. It influences glucose metabolism, suppresses inflammation, modulates the immune system, and helps the body respond to physical and psychological stress.


ACTH, as a key hormone in the HPA axis, plays a vital role in regulating the production of cortisol by the adrenal glands. It is essential for maintaining homeostasis, responding to stress, and ensuring proper metabolic and immune function. Understanding the function of ACTH provides insights into the complex interplay between the hypothalamus, pituitary gland, and adrenal glands, contributing to our knowledge of endocrine physiology.

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