It starts in the brain. The hypothalamus sends signals. In response, corticotropin-releasing hormone (CRH) is released. This small molecule reaches the pituitary gland. The pituitary gland, specifically cells called corticotrophs, pumps out adrenocorticotropic hormone (ACTH).
This is more than just a switch. ACTH is a fragment of a larger molecule called proopiomelanocortin (POMC). About 10% of the pituitary gland is consists of these corticotrophs. They synthesize POMC. When secretory granules are discharged, the large molecule splits. It breaks into several active polypeptides.
ACTH is one of them. Its main function is simple. It targets the cortex of the adrenal gland. In particular, it regulates the extrinsic regions that produce glucocorticoids. In mammals, this means cortisol and corticosterone. This hormone stimulates the growth of adrenal cells. It also drives them to secrete more cortisol.
But things get complicated when you look at the rest of the POMC. Because ACTH is only one piece of the puzzle, the other pieces are released at the same time. This can have far-reaching effects beyond the stress response.
ACTH is part of a larger glycoprotein prohormone molecule called proopiomelanocortin (POMC). When released, this molecule splits into several biologically active peptides.
More Than Just Stress
You may be familiar with ACTH’s role in the stress response. But why does it affect skin color? Or pain? Or memory?
The answer lies in its siblings. The splitting of POMC releases more than just ACTH. It releases alpha- and beta-melanotropin. These increase skin pigmentation. This is why high ACTH concentrations cause skin darkening.
It also releases beta-lipotropin. This stimulates the release of fatty acids from adipose tissue. It involves the mobilization of energy.
Then there is beta-endorphin. This fragment suppresses pain. It is a natural opioid.
Some researchers believe that low doses of ACTH can improve memory. The evidence is less clear here. However, the relationship between stress hormones and cognitive function is a hot topic. The body does not neatly divide these functions. They are intertwined.
When the System Breaks
What happens when the pituitary gland loses control?
When tumors develop in adrenocorticotrophic cells or when adrenocorticotrophic cells become hyperplastic, ACTH secretion increases rapidly. The adrenal glands react by producing too much cortisol. This leads to adrenocortical hyperfunction. The result is a cluster of symptoms known as Cushing syndrome.
Patients experience weight gain, high blood pressure and thinning of the skin. Excessive ACTH can also cause significant skin pigmentation. This is an important diagnostic clue. If a patient has Cushing-like symptoms but dark skin, doctors look for an ACTH-secreting tumor. This is different from Cushing’s disease, where the adrenal glands themselves cause low ACTH levels.
ACTH deficiency, on the other hand, is dangerous. It can occur as part of panhypopituitarism. This is a malfunction of several pituitary hormones. Or it can happen
