Urocortin is a protein that in humans is encoded by the UCN gene. Urocortin belongs to the corticotropin-releasing factor (CRF) family of proteins which includes CRF, urotensin I, sauvagine, urocortin II and urocortin III. Urocortin is involved in the mammalian stress response, and regulates aspects of appetite and stress response. [5] [6] [7]
Urocortin is a peptide composed of 40 amino acids. Urocortin is composed of a single alpha helix structure. The human UCN gene contains two exons, and the entirety of the coding region is contained within the second exon. [5] Urocortin is expressed widely in the central and peripheral nervous systems, with a pattern similar to that of CRF. [8] Areas of similarity between urocortin and CRF expression include the supraoptic nucleus and the hippocampus. [9] [10] Urocortin is also expressed in areas distinct from CRF expression; these areas notably include the median eminence, the Edinger-Westphal nucleus, and the sphenoid nucleus. [10] Additionally, Urocortin is expressed in peripheral tissues such as the heart. [11]
Urocortin is known to interact both with the CRF type 1 and CRF type 2 receptors. [12] [13] [14] Furthermore, Urocortin is thought to be the primary ligand for the CRF type 2 receptor, as it has higher binding affinity for the CRF type 2 receptor than CRF. [12] Additionally, urocortin interacts with CRF Binding Protein in the mammalian brain. [15]
Urocortin is closely related to CRF, which mediates the mammalian stress response. Urocortin is consequently implicated in a number of stress responses, primarily relating to appetite and food intake. Administration of urocortin to the central nervous system of mice and rats has been shown to decrease appetite. [16] Additionally, central urocortin treatment increases anxiety-linked behaviors and increases motor activity in mice and rats. [16] These general anxiety-linked behaviors are likely induced through the CRF type 1 receptor, and the appetite behaviors are likely induced through the CRF type 2 receptor. The reduction in appetite from urocortin treatment could be a result of suppression of gastric emptying and/or hypoglycemia, which have been shown to result from urocortin treatment. [17] Urocortin expression is stimulated in response to osmotic stress; water deprivation in rats has been shown to induce urocortin expression in the supraoptic nucleus. [18]
Montane Voles and Meadow Voles are closely related species of voles which are regularly studied as a model for social and mating behavior. The distribution of urocortin-expressing neurons differs in meadow voles compared to montane voles, suggesting urocortin may also play a role in modulating social behavior in some species. [19]
Urocortin has been shown to induce increases in heart rate and coronary blood flow when applied peripherally. [11] These effects are likely mediated through the CRF type 2 receptor, as this receptor is found in the cardiac atria and ventricles. [20] Urocortin also functions to protect cardiovascular tissue from ischemic injury. [21] Urocortin's cardiovascular effects separate it from other members of the CRF family, and likely represent its primary biological function.
Urocortin is not present in all non-mammals; the closet analogue in teleost fish is urotensin I. [22] However, in amphibian species such as Xenopus laevis , urocortin is expressed in tissues such as brain, pituitary, kidney, heart, and skin. Urocortin in Xenopus has been shown to increase cAMP accumulation and inhibit appetite [22]
Corticotropin-releasing hormone (CRH) is a peptide hormone involved in stress responses. It is a releasing hormone that belongs to corticotropin-releasing factor family. In humans, it is encoded by the CRH gene. Its main function is the stimulation of the pituitary synthesis of adrenocorticotropic hormone (ACTH), as part of the hypothalamic–pituitary–adrenal axis.
Corticotropin-releasing factor family, CRF family is a family of related neuropeptides in vertebrates. This family includes corticotropin-releasing hormone, urotensin-I, urocortin, and sauvagine. The family can be grouped into 2 separate paralogous lineages, with urotensin-I, urocortin and sauvagine in one group and CRH forming the other group. Urocortin and sauvagine appear to represent orthologues of fish urotensin-I in mammals and amphibians, respectively. The peptides have a variety of physiological effects on stress and anxiety, vasoregulation, thermoregulation, growth and metabolism, metamorphosis and reproduction in various species, and are all released as prohormones.
Ghrelin is a hormone primarily produced by enteroendocrine cells of the gastrointestinal tract, especially the stomach, and is often called a "hunger hormone" because it increases the drive to eat. Blood levels of ghrelin are highest before meals when hungry, returning to lower levels after mealtimes. Ghrelin may help prepare for food intake by increasing gastric motility and stimulating the secretion of gastric acid.
Urocortin 2 (Ucn2) is an endogenous peptide in the corticotrophin-releasing factor (CRF) family.
Urocortin III, a 38–41 amino acid peptide, is a member of the CRF, also known as CRH family of peptides, with a long evolutionary lineage.
The secretin receptor is a protein that in humans is encoded by the SCTR gene. This protein is a G protein-coupled receptor which binds secretin and is the leading member of the secretin receptor family, also called class B GPCR subfamily.
The adrenocorticotropic hormone receptor or ACTH receptor also known as the melanocortin receptor 2 or MC2 receptor is a type of melanocortin receptor (type 2) which is specific for ACTH. A G protein–coupled receptor located on the external cell plasma membrane, it is coupled to Gαs and upregulates levels of cAMP by activating adenylyl cyclase. The ACTH receptor plays a role in immune function and glucose metabolism.
Parathyroid hormone/parathyroid hormone-related peptide receptor, also known as parathyroid hormone 1 receptor (PTH1R), is a protein that in humans is encoded by the PTH1R gene. PTH1R functions as a receptor for parathyroid hormone (PTH) and for parathyroid hormone-related protein (PTHrP), also called parathyroid hormone-like hormone (PTHLH).
Corticotropin-releasing hormone receptor 1 (CRHR1) is a protein, also known as CRF1, with the latter (CRF1) now being the IUPHAR-recommended name. In humans, CRF1 is encoded by the CRHR1 gene at region 17q21.31, beside micrototubule-associated protein tau MAPT.
Corticotropin-releasing hormone receptor 2 (CRHR2) is a protein, also known by the IUPHAR-recommended name CRF2, that is encoded by the CRHR2 gene and occurs on the surfaces of some mammalian cells. CRF2 receptors are type 2 G protein-coupled receptors for corticotropin-releasing hormone (CRH) that are resident in the plasma membranes of hormone-sensitive cells. CRH, a peptide of 41 amino acids synthesized in the hypothalamus, is the principal neuroregulator of the hypothalamic-pituitary-adrenal axis, signaling via guanine nucleotide-binding proteins (G proteins) and downstream effectors such as adenylate cyclase. The CRF2 receptor is a multi-pass membrane protein with a transmembrane domain composed of seven helices arranged in a V-shape. CRF2 receptors are activated by two structurally similar peptides, urocortin II, and urocortin III, as well as CRH.
Corticotropin-releasing factor-binding protein is a protein that in humans is encoded by the CRHBP gene. It belongs to corticotropin-releasing hormone binding protein family.
Urocortin-2 is a protein that in humans is encoded by the UCN2 gene.
Urocortin-3 is a protein that, in humans, is encoded by the UCN3 gene. It belongs to the corticotropin-releasing hormone family.
Prolactin-releasing peptide (PrRP) is a peptide hormone that in humans is encoded by the PRLH gene. PrRP stimulates prolactin (PRL) release and regulates the expression of prolactin through binding to the prolactin-releasing peptide receptor (GPR10).
Antalarmin (CP-156,181) is a drug that acts as a CRH1 antagonist.
A Corticotropin-releasing hormone antagonist is a specific type of receptor antagonist that blocks the receptor sites for corticotropin-releasing hormone, also known as corticotropin-releasing factor (CRF), which synchronizes the behavioral, endocrine, autonomic, and immune responses to stress by controlling the hypothalamic-pituitary-adrenal axis. CRH antagonists thereby block the consequent secretions of ACTH and cortisol due to stress, among other effects.
BIBP-3226 is a drug used in scientific research which acts as a potent and selective antagonist for both the Neuropeptide Y receptor Y1 and also the neuropeptide FF receptor. It was the first non-peptide antagonist developed for the Y1 receptor and has been widely used to help determine its functions in the body. Activation of Y1 is thought to be involved in functions such as regulation of appetite and anxiety, and BIBP-3226 has anxiogenic and anorectic effects, as well as blocking the Y1-mediated corticotropin releasing hormone release. It has also been used as a lead compound to develop a number of newer more potent Y1 antagonists.
Corticotropin-releasing hormone binding protein (CRH-BP) binds corticotropin-releasing hormone (CRH) and several related peptide hormones. It is an ancient, highly conserved protein whose origin predates the divergence of protostomes and deuterostomes.
Astressin-B is a nonselective corticotropin releasing hormone antagonist that reduces the synthesis of adrenocorticotropic hormone and cortisol.
Sauvagine is a neuropeptide from the corticotropin-releasing factor (CRF) family of peptides and is orthologous to the mammalian hormone, urocortin 1, and the teleost fish hormone, urotensin 1. It is 40 amino acids in length, and has the sequence XGPPISIDLSLELLRKMIEIEKQEKEKQQAANNRLLLDTI-NH2, with a pyrrolidone carboxylic acid modification at the N-terminal and amidation of the C-terminal isoleucine residue. It was originally isolated from the skin of the frog Phyllomedusa sauvagii. Given its relation to other CRF-related peptides, it exerts similar physiological effects as corticotropin-releasing hormone.
