Adrenocorticotropic hormone (ACTH) and cortisol are powerful chemical messengers central to the body’s stress response. ACTH is a signaling molecule released in the brain that directs the adrenal glands to produce cortisol. Cortisol, often called the “stress hormone,” is a steroid that regulates numerous bodily processes and prepares the system for action. Together, these hormones govern the physiological cascade that enables the body to adapt and survive under physical or psychological demand.
The HPA Axis: How ACTH Regulates Cortisol Production
The control system dictating cortisol release is the multi-step Hypothalamic-Pituitary-Adrenal (HPA) axis. This process begins when the hypothalamus detects a stressor or is signaled by the body’s circadian rhythm. In response, the hypothalamus releases Corticotropin-releasing hormone (CRH), which initiates the regulatory chain.
CRH travels to the pituitary gland, situated beneath the brain. Upon receiving the CRH signal, specialized cells in the anterior pituitary synthesize and secrete Adrenocorticotropic hormone (ACTH) into the bloodstream. ACTH carries the signal from the brain to the hormone-producing glands.
ACTH circulates until it reaches the adrenal glands, two small structures atop the kidneys. It binds to receptors on the adrenal cortex, specifically targeting the zona fasciculata. This binding stimulates the synthesis of cortisol from cholesterol, the final step in the HPA axis cascade.
As cortisol levels rise, the hormone exerts a negative feedback effect on the HPA axis to prevent overproduction. Cortisol signals back to the hypothalamus and pituitary gland, inhibiting the further release of CRH and ACTH. This loop ensures cortisol production is tightly controlled, allowing the body to return to balance once the stressor passes.
Essential Functions of Cortisol in the Body
Once released, cortisol affects nearly every organ system, managing energy and modulating the immune response. A primary action is mobilizing energy reserves to support the “fight-or-flight” state. Cortisol increases glucose availability for the brain by promoting gluconeogenesis in the liver.
This metabolic function creates new glucose molecules from non-carbohydrate sources like amino acids and fats. Cortisol inhibits glucose uptake by muscle and fat cells, reserving circulating sugar for the central nervous system. It also stimulates the breakdown of stored fat (lipolysis) and protein (protein catabolism) to provide necessary building blocks.
Cortisol is a modulator of the immune system, acting as an anti-inflammatory agent. This prevents an overreaction of the body’s defenses to injury or infection. Cortisol achieves this by suppressing pro-inflammatory transcription factors, such as NF-kB, and reducing white blood cell migration to inflammation sites.
This function limits tissue damage resulting from prolonged inflammation. In the cardiovascular system, cortisol works with adrenaline to maintain blood pressure and vascular tone. These effects ensure the body has sufficient energy, controlled inflammation, and stable circulation to respond to stress.
Health Conditions Caused by Imbalance
Chronic dysregulation of the ACTH-cortisol system leads to health conditions characterized by hormone excess or deficiency.
Hypercortisolism (Cushing’s Syndrome)
Hypercortisolism, or persistently high cortisol levels, is categorized as Cushing’s Syndrome. This condition results in symptoms related to cortisol’s functions, such as elevated blood glucose and fat tissue redistribution. Cushing’s Syndrome often presents with central obesity, a rounded “moon face,” and muscle weakness due to protein breakdown.
If the excess cortisol is traced to an ACTH-producing tumor in the pituitary gland, it is specifically called Cushing’s Disease. Cushing’s Syndrome can also be caused by long-term use of synthetic glucocorticoid medications or a tumor in the adrenal gland itself.
Hypocortisolism (Adrenal Insufficiency)
The opposite imbalance, Hypocortisolism or adrenal insufficiency, occurs when the adrenal glands do not produce enough cortisol. The primary form is Addison’s Disease, often caused by an autoimmune response that damages the adrenal cortex. Symptoms reflect the body’s inability to mount a stress response, including persistent fatigue, unintentional weight loss, and low blood pressure.
In Addison’s Disease, the pituitary gland compensates for low cortisol by significantly increasing ACTH production. Since ACTH is derived from a precursor molecule that also creates melanocyte-stimulating hormone (MSH), high ACTH levels can cause distinct skin darkening. Secondary adrenal insufficiency involves low cortisol resulting from insufficient ACTH release from the pituitary gland.