Polypeptide hormone made in the pituitary gland. It regulates the activity of part of the adrenal cortex (see adrenal glands), the production site of important steroid hormones that affect electrolyte and water balance and the metabolism of fats, carbohydrates, and proteins. ACTH is found in vertebrates (except jawless fishes); in mammals it contains 39 amino acids. Overproduction of ACTH is one cause of Cushing syndrome.
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Corticotropin-releasing hormone (CRH) is a 41-amino acid peptide derived from a 191-amino acid preprohormone. CRH is secreted by the paraventricular nucleus (PVN) of the hypothalamus in response to stress. Marked reduction in CRH has been observed in association with Alzheimer's disease, and autosomal recessive hypothalamic corticotropin deficiency has multiple and potentially-fatal metabolic consequences including hypoglycemia and hepatitis. In addition to being produced in the hypothalamus, CRH is also synthesized in peripheral tissues, such as T lymphocytes, and is highly expressed in the placenta. In the placenta, CRH is a marker that determines the length of gestation and the timing of parturition and delivery. A rapid increase in circulating levels of CRH occurs at the onset of parturition, suggesting that, in addition to its metabolic functions, CRH may act as a trigger for parturition.
α-helical CRH-(9–41) acts as a CRH antagonist.
Also, abnormal levels of CRH have been found in the cerebrospinal fluid of suicide victims.
Recent research has linked the activation of the CRH1 receptor with the euphoric feelings that accompany alcohol consumption. A CRH1 receptor antagonist developed by Pfizer, CP-154,526 is under investigation for the potential treatment of alcoholism.
Levels rise towards birth and current theory suggests three roles of CRH in parturition:
In culture, trophoblast CRH is inhibited by progesterone, which remains high throughout pregnancy. Its release is stimultated by glucocorticoids and catecholamines, which increase prior to parturition lifting this progesterone block.