ACTH is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress (along with its precursor corticotropin-releasing hormone from the hypothalamus).

In Cushing's disease, a pituitary tumor leads to excessive production of ACTH, which stimulates the adrenal cortex to produce high levels of cortisol.

[6][7][8] ACTH consists of 39 amino acids, the first 13 of which (counting from the N-terminus) may be cleaved to form α-melanocyte-stimulating hormone (α-MSH) (this common structure is responsible for excessively tanned skin in Addison's disease).

After a short period of time, ACTH is cleaved into α-melanocyte-stimulating hormone (α-MSH) and CLIP, a peptide with unknown activity in humans.

[10] Upon ligand binding, the receptor undergoes conformation changes that stimulate the enzyme adenylyl cyclase, which leads to an increase in intracellular cAMP[11] and subsequent activation of protein kinase A. ACTH influences steroid hormone secretion by both rapid short-term mechanisms that take place within minutes and slower long-term actions.

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

The long term actions of ACTH include stimulation of the transcription of the genes coding for steroidogenic enzymes, especially P450scc, steroid 11β-hydroxylase, and their associated electron transfer proteins.

[15] Since that time, it has been demonstrated that the response of bone forming cells to ACTH includes production of VEGF, as it does in the adrenal.

While working on her dissertation, Evelyn M. Anderson co-discovered ACTH with James Bertram Collip and David Landsborough Thomson and, in a paper published in 1933, explained its function in the body.