ACTH

= Adrenocorticotropic Hormone (ACTH) =

Adrenocorticotropic hormone (ACTH), also known as corticotropin, is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It plays a crucial role in the stress response and in the regulation of adrenal gland function.

Structure and Synthesis

ACTH is a peptide hormone consisting of 39 amino acids. It is derived from the precursor molecule proopiomelanocortin (POMC), which is synthesized in the corticotroph cells of the anterior pituitary. The cleavage of POMC yields several peptides, including ACTH, β-endorphin, and melanocyte-stimulating hormones (MSH).

Regulation of Secretion

The secretion of ACTH is primarily regulated by the hypothalamic-pituitary-adrenal (HPA) axis. Corticotropin-releasing hormone (CRH) is released from the hypothalamus in response to stress and circadian rhythms. CRH stimulates the anterior pituitary to secrete ACTH. In turn, ACTH stimulates the adrenal cortex to produce glucocorticoids, primarily cortisol.

Cortisol exerts negative feedback on both the hypothalamus and the pituitary gland to inhibit further release of CRH and ACTH, respectively. This feedback loop helps maintain homeostasis and regulate the body's response to stress.

Function

ACTH primarily acts on the adrenal cortex, where it binds to the melanocortin 2 receptor (MC2R) on the surface of adrenocortical cells. This binding stimulates the production and release of glucocorticoids, mineralocorticoids, and androgens.

Glucocorticoids

The main glucocorticoid produced in response to ACTH is cortisol. Cortisol has numerous physiological effects, including:

• Increasing blood glucose levels by promoting gluconeogenesis in the liver.
• Suppressing the immune response and inflammation.
• Aiding in fat, protein, and carbohydrate metabolism.
• Helping the body respond to stress.

Mineralocorticoids

While ACTH has a minor role in the regulation of mineralocorticoids, it can influence the production of aldosterone, which is primarily regulated by the renin-angiotensin system. Aldosterone helps regulate blood pressure by controlling sodium and water balance in the kidneys.

Androgens

ACTH also stimulates the production of adrenal androgens, such as dehydroepiandrosterone (DHEA), which serve as precursors to sex hormones.

Clinical Significance

Disorders of ACTH Secretion

• Cushing's Disease: This condition is characterized by excessive production of ACTH, usually due to a pituitary adenoma, leading to overproduction of cortisol by the adrenal glands. Symptoms include weight gain, hypertension, and glucose intolerance.

• Addison's Disease: This is a condition where there is insufficient production of cortisol due to adrenal insufficiency. It can be caused by inadequate ACTH production or adrenal gland dysfunction. Symptoms include fatigue, weight loss, and hypotension.

• ACTH Stimulation Test: This test is used to assess adrenal gland function by measuring cortisol response to synthetic ACTH administration.

Conclusion

ACTH is a vital hormone in the regulation of the body's response to stress and in maintaining homeostasis through its effects on the adrenal cortex. Understanding its synthesis, regulation, and function is crucial for diagnosing and managing disorders related to the HPA axis.