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Physiology of corticotropin-releasing hormone

George P Chrousos, MD
Section Editor
André Lacroix, MD
Deputy Editor
Kathryn A Martin, MD


A hypothalamic factor that increases corticotropin (ACTH) release from pituitary cells was discovered as an active principle in 1955 [1,2]. In 1981, ovine corticotropin-releasing hormone (CRH) was isolated and sequenced [3].

CRH is a 41-amino acid peptide that is the major physiologic ACTH secretagogue [4,5]. There is considerable sequence homology of CRH among species, particularly in the amino-terminal region, which is required for biologic activity. CRH belongs to a family of peptides that includes the nonmammalian sauvagine and urotensin I, the mammalian urocortins 1, 2 (stresscopin-related peptide, SRP), and 3 (stresscopin, SCP), the last three of which also are found in humans [6-8]. All of these peptides have activities similar to but also distinct from those of CRH [7].

CRH is processed from a prepro-CRH molecule (196 amino acids in humans) from which it is cleaved at flanking basic amino acid pairs [9]. The single human CRH gene is located on chromosome 8 [10], those of human urocortins 1, 2, and 3 on chromosomes 2, 3, and 10 respectively [8].


Corticotropin-releasing hormone (CRH) is synthesized by neurons in the parvocellular (small cell) division of the hypothalamic paraventricular nuclei [11]. Their axons project to the median eminence, where CRH is secreted into the hypophysial portal blood. These neurons may also contain other corticotropin (ACTH) secretagogues (eg, arginine vasopressin [12] and cholecystokinin [13]), opioid peptides (eg, met-enkephalin [14] and dynorphin-1-8 [15]), and PHI-27, a prolactin secretagogue [14], particularly after adrenalectomy. In addition, CRH is synthesized by anterior pituitary corticotrophs and acts in an autocrine or paracrine manner to stimulate ACTH secretion [16].

CRH is also present in some oxytocin-containing neurons in the magnocellular (large cell) division of the paraventricular nuclei that project to the posterior pituitary [17]. In addition, CRH is widely distributed throughout the brain and spinal cord [11,18] and in peripheral tissues, such as the adrenal medulla [19], testis [20], ovaries [21], gastrointestinal tract [22,23], pancreas [24], skin [25], myometrium [26], endometrium [27], and placenta [28].


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Literature review current through: Sep 2016. | This topic last updated: May 8, 2015.
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