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Adrenocorticotropic hormone is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress. Its principal effects are increased production and release of cortisol and androgens by the zona fasiculata and zona reticularis, respectively. ACTH is also related to the circadian rhythm in many organisms.
Pro-opiomelanocortin (POMC) is a precursor polypeptide with 241 amino acid residues. POMC is synthesized in corticotrophs of the anterior pituitary from the 267-amino-acid-long polypeptide precursor pre-pro-opiomelanocortin (pre-POMC), by the removal of a 26-amino-acid-long signal peptide sequence during translation. POMC is part of the central melanocortin system.
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.
Peptide hormones are hormones whose molecules are peptides. Peptide hormones have shorter amino acid chain lengths than protein hormones. These hormones have an effect on the endocrine system of animals, including humans. Most hormones can be classified as either amino acid–based hormones or steroid hormones. The former are water-soluble and act on the surface of target cells via second messengers; the latter, being lipid-soluble, move through the plasma membranes of target cells to act within their nuclei.
The posterior pituitary is the posterior lobe of the pituitary gland which is part of the endocrine system. The posterior pituitary is not glandular as is the anterior pituitary. Instead, it is largely a collection of axonal projections from the hypothalamus that terminate behind the anterior pituitary, and serve as a site for the secretion of neurohypophysial hormones directly into the blood. The hypothalamic–neurohypophyseal system is composed of the hypothalamus, posterior pituitary, and these axonal projections.
The paraventricular nucleus is a nucleus in the hypothalamus. Anatomically, it is adjacent to the third ventricle and many of its neurons project to the posterior pituitary. These projecting neurons secrete oxytocin and a smaller amount of vasopressin, otherwise the nucleus also secretes corticotropin-releasing hormone (CRH) and thyrotropin-releasing hormone (TRH). CRH and TRH are secreted into the hypophyseal portal system and act on different targets neurons in the anterior pituitary. PVN is thought to mediate many diverse functions through these different hormones, including osmoregulation, appetite, and the response of the body to stress.
Corticotropes are basophilic cells in the anterior pituitary that produce pro-opiomelanocortin (POMC) which undergoes cleavage to adrenocorticotropin (ACTH), β-lipotropin (β-LPH), and melanocyte-stimulating hormone (MSH). These cells are stimulated by corticotropin releasing hormone (CRH) and make up 15–20% of the cells in the anterior pituitary. The release of ACTH from the corticotropic cells is controlled by CRH, which is formed in the cell bodies of parvocellular neurosecretory cells within the paraventricular nucleus of the hypothalamus and passes to the corticotropes in the anterior pituitary via the hypophyseal portal system. Adrenocorticotropin hormone stimulates the adrenal cortex to release glucocorticoids and plays an important role in the stress response.
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.
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.
Corticotropin-releasing hormone receptors (CRHRs), also known as corticotropin-releasing factor receptors (CRFRs) are a G protein-coupled receptor family that binds corticotropin-releasing hormone (CRH). There are two receptors in the family, designated as type 1 and 2, each encoded by a separate gene.
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.
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.
Parvocellular neurosecretory cells are small neurons that produce hypothalamic releasing and inhibiting hormones. The cell bodies of these neurons are located in various nuclei of the hypothalamus or in closely related areas of the basal brain, mainly in the medial zone of the hypothalamus. All or most of the axons of the parvocellular neurosecretory cells project to the median eminence, at the base of the brain, where their nerve terminals release the hypothalamic hormones. These hormones are then immediately absorbed into the blood vessels of the hypothalamo-pituitary portal system, which carry them to the anterior pituitary gland, where they regulate the secretion of hormones into the systemic circulation.
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.
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.
References
- ↑ Balment RJ, Lovejoy DA (1999). "Evolution and physiology of the corticotropin-releasing factor (CRF) family of neuropeptides in vertebrates". Gen. Comp. Endocrinol. 115 (1): 1–22. doi:10.1006/gcen.1999.7298. PMID 10375459.
- ↑ Lederis KP, Okawara Y, Richter D, Morley SD (1990). "Evolutionary aspects of corticotropin releasing hormones". Prog. Clin. Biol. Res. 342: 467–472. PMID 2200028.
- ↑ Vale, Wylie; Rivier, Catherine; Brown, Marvin R.; Spies, Joachim; Koob, George; Swanson, Larry; Bilezikjian, Louise; Bloom, Floyd; Rivier, Jean (1983). "Chemical and Biological Characterization of Corticotropin Releasing Factor". Proceedings of the 1982 Laurentian Hormone Conference. Vol. 39. pp. 245–270. doi:10.1016/B978-0-12-571139-5.50010-0. ISBN 978-0-12-571139-5. PMID 6314446.
{{cite book}}:|journal=ignored (help) - ↑ Erspamer, V.; Erspamer, G. Falconieri; Improta, G.; Negri, L.; de Castiglione, R. (July 1980). "Sauvagine, a new polypeptide from Phyllomedusa sauvagei skin: Occurrence in various phyllomedusa species and pharmacological actions on rat blood pressure and diuresis". Naunyn-Schmiedeberg's Archives of Pharmacology. 312 (3): 265–270. doi:10.1007/BF00499156. PMID 7402368. S2CID 22509929.