Adrenocorticotropic Hormone

The adrenocorticotropic hormone is considered an important hormone for the functioning of the adrenal gland. It stimulates the production of a stress hormone called cortisol from the cortex of the adrenal gland. It is secreted by corticotroph cells of the anterior pituitary gland.

The primary function of the adrenocorticotropic hormone is to stimulate the secretion of glucocorticoids. It has some control over aldosterone, a hormone produced by the adrenal gland. The adrenocorticotropic hormones are high during the day when we wake up and fall as the day passes and are lowest when we sleep. This rhythm is called the diurnal rhythm.

Molecular structure of adrenocorticotropic hormone 

The molecular weight of adrenocorticotropic hormone is 5250 and is composed of 39 amino acids in a single chain. There is no disulphide linkage in a single chain.

Production of adrenocorticotropic hormone

The hypothalamus of the brain produces the corticotropin-releasing hormone, which stimulates the basophils cells of the pituitary gland to produce adrenocorticotropic hormone (ACTH). It is secreted into the bloodstream, where it travels to the adrenal gland.

Once it reaches the adrenal gland, it allows more secretion of cortisol by binding itself to the receptors of adrenal glands. As a result of increased production, there is a rise in blood cortisol levels. The rise in cortisol slows down the production of corticotropin-releasing hormone from the hypothalamus and adrenocorticotropic hormone from the pituitary gland. This is called a negative feedback loop.

Control of adrenocorticotropic hormone 

The secretion of adrenocorticotropic hormone in the body is controlled by the hypothalamus, the pituitary and adrenal glands. This control region is called the hypothalamus-pituitary-adrenal (HPA) axis.

Functions of adrenocorticotropic hormone

• It regulates metabolism
• It helps in maintaining blood pressure.
• It produces steroids to help respond to stress.
• It helps to fight infections.
• It regulates the blood sugar level.
• It aids protein catabolism.
• It is responsible for spermatogenesis in men.
• It helps in lipolysis.
• It aids bone resorption.

Pathophysiology

Pathophysiology of adrenocorticotropic hormone is related to disturbance in one of the three mechanisms — pituitary, adrenal or ectopic secretion.

The hypofunctioning or hyperfunctioning of the pituitary gland results in decreased or increased ACTH. The most common cause responsible for pituitary malfunctioning is an adenoma. Pituitary apoplexy, sudden bleeding into a pituitary tumour, can also cause an abrupt depletion of ACTH. Pituitary insufficiency can also be caused by Sheehan syndrome, which happens less often.

The adrenal glands can be either hypo- or hyperactive. Addison’s disease and Cushing’s disease are both adrenal diseases.

The creation of a hormone outside of its typical physiological mechanism is referred to as ectopic secretion. The hormone is secreted by both benign and malignant tumours. Normal feedback loop mechanisms do not control hormone production. Ectopic ACTH production is linked to Cushing syndrome.

Clinical significance of adrenocorticotropic hormone

• Addison disease: It is an autoimmune disease that involves the destruction of three layers of adrenal cortex. This destruction can be due to congenital enzyme deficiency or autoimmune disorders. The destruction causes a decrease in the production of adrenocorticotropic hormone, which decreases the production of steroids and mineralocorticoids. The common symptoms of Addison disease are weakness, fatigue, nausea and vomiting.

• Hypercortisolism: Exogenous glucocorticoids lead to increased production of adrenal cortisol as a result of ectopic production of adrenocorticotropic hormone. Cortisol is a mandatory hormone for the metabolism of glucose and plays an important role in the immune system. The common symptoms found in hypercortisolism are diabetes mellitus due to insulin resistance and dyslipidemia due to alteration in glucose metabolism.
• West syndrome: It occurs in infants below the age of 12 months. The key symptoms are sudden spasm of neck, trunk and extremities. However, its direct relation to adrenocorticotropic hormone is unknown.

Hormones level and risk factor

The normal range of adrenocorticotropic hormone varies with respect to age and sex between 6.0 and 76 pg/ml

Increased production of adrenocorticotropic hormone

High levels of adrenocorticotropic hormones are definitely due to an increase in the level of cortisol produced by adrenal glands. These high level of adrenocorticotropic hormone may be due to:

• Cushing disease. It is an adenoma or non-cancerous tissue present at the pituitary gland. It leads to an increase in production of adrenocorticotropic hormone.
• Tumour growth outside the pituitary gland, which produces adrenocorticotropic hormone also called ectopic ACTH. 
• Congenital adrenal hyperplasia

Decreased production of adrenocorticotropic hormone

Less production of adrenocorticotropic hormone can affect the functioning of the adrenal gland. Poorly functioning adrenal gland leads to insufficient amounts of cortisol. Decreased production of cortisol ultimately leads to metabolic disorders. Lower level of adrenocorticotropic hormone may be due to:

• Hypopituitarism 
• A side effect of radiation therapy 
• A side effect of pituitary surgery
• Long term use of steroids

Conclusion 

Adrenocorticotropic hormone (ACTH) is secreted by the pituitary gland and controlled by the hypothalamus-pituitary axis. It regulates the production of cortisol and androgen by the adrenal glands.when, pituitary gland secretes adrenocorticotropic hormone, which binds to the receptor of adrenal glands to produce cortisol from the adrenal cortex. It is controlled by the hypothalamus-pituitary-adrenal gland (HPA) axis. Severe increase or decrease of the adrenocorticotropic hormone can cause severe health conditions.