Adrenocorticotropic hormone

Adrenocorticotropic hormone (ACTH, also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland.

ACTH can be used as a medication and diagnostic agent.

It is important component of the hypothalamic-pituitary-adrenal axis.

ACTH is often produced in response to biological stress, along with its precursor corticotropin-releasing hormone from the hypothalamus.

Its main effects are production and release of cortisol by the cortex of the adrenal gland.

ACTH is a hormone produced in the anterior pituitary gland that stimulates the adrenal glands to release cortisol, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and aldosterone.

Deficiency of ACTH is a sign of secondary adrenal insufficiency or tertiary adrenal insufficiency.

Chronically elevated ACTH levels occur in primary adrenal insufficiency when adrenal gland production of cortisol is chronically deficient.

In Cushing’s disease a pituitary tumor is the cause of elevated ACTH and an excess of cortisol.

The above constellation of signs and symptoms is known as Cushing’s syndrome.

POMC, ACTH and ?-lipotropin are secreted from corticotropes in the anterior lobe of the pituitary gland in response to the hormone corticotropin-releasing hormone (CRH) released by the hypothalamus.

ACTH is synthesized from pre-pro-opiomelanocortin (pre-POMC).

The removal of the signal peptide during translation from prePOMP produces the 241-amino acid polypeptide POMC, which undergoes a series of post-translational modifications such as phosphorylation and glycosylation before it is proteolytically cleaved by endopeptidases to yield various polypeptide fragments with varying physiological activity.

These polypeptide fragments include: ACTH, and melanocyte-stimulating hormone among others.

To regulate the secretion of ACTH, many substances secreted within this axis exhibit slow/intermediate and fast feedback-loop activity.

Glucocorticoids secreted from the adrenal cortex work to inhibit CRH secretion by the hypothalamus, which in turn decreases anterior pituitary secretion of ACTH.

The half-life of ACTH in human blood is about ten minutes.

ACTH consists of 39 amino acids, the first 13 of which may be cleaved to form ?-melanocyte-stimulating hormone (?-MSH), that is responsible for excessively tanned skin in Addison’s disease.

ACTH stimulates secretion of glucocorticoid steroid hormones from adrenal cortex cells, especially in the zona fasciculata of the adrenal glands.

ACTH acts by binding to cell surface ACTH receptors, which are located primarily on adrenocortical cells of the adrenal cortex.

The ACTH receptor is a seven-membrane-spanning G protein-coupled receptor.

Upon ligand binding, the receptor undergoes changes that leads to an increase in intracellular cAMPand subsequent activation of protein kinase A.

Rapid actions of ACTH include stimulation of cholesterol delivery to the mitochondria where the P450scc enzyme is located.

P450scc catalyzes the first step of steroidogenesis of cholesterol, and also stimulates lipoprotein uptake into cortical cells, increasing the bioavailability of cholesterol in the cells of the adrenal cortex.

It has an activating effect on melanocyte Stephen hormone receptors so that high levels spurs production of melanin and subsequent discoloration of the skin or mucosa.

The long term actions of ACTH include stimulation of genes coding for steroidogenic enzymes, and enhances transcription of mitochondrial genes that encode for subunits of mitochondrial oxidative phosphorylation systems.

It is a cleavage product of the pro-hormone, proopiomelanocortin (POMC).

Proopiomelanocortin (POMC) also produces other hormones including ?-MSH that stimulates the production of melanin.

A family of related receptors mediates the actions of these hormones,

The MCR, or melanocortin receptor family mediates the actions of these hormones.

MC2R is the ACTH receptor.

MC2R ACTH receptor regulates the adrenal gland, is expressed in the osteoblast, which is responsible for making new bone.

The response of bone forming cells to ACTH includes production of VEGF, as it does in the adrenal.

Diseases of the pituitary, the gland that produces ACTH.

Hypopituitarism, the hyposecretion of ACTH in the pituitary, leading to secondary adrenal insufficiency.

Addison’s disease, the primary adrenal insufficiency.

Cushing’s syndrome, hypercorticism, one of the causes is hypersecretion of ACTH

Small cell carcinoma, a common cause of ACTH secreted ectopically.

Congenital adrenal hyperplasia, diseases in the production of cortisol

Nelson’s syndrome, the rapid enlargement of the ACTH producing pituitary after the removal of both adrenal glands.

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