9015-71-8

Basic information

• Product Name: CRF (OVINE)
• Synonyms: SQEPPISLDLTFHLLREVLEMTKADQLAQQAHSNRKLLDIA-NH2;SER-GLN-GLU-PRO-PRO-ILE-SER-LEU-ASP-LEU-THR-PHE-HIS-LEU-LEU-ARG-GLU-VAL-LEU-GLU-MET-THR-LYS-ALA-ASP-GLN-LEU-ALA-GLN-GLN-ALA-HIS-SER-ASN-ARG-LYS-LEU-LEU-ASP-ILE-ALA-NH2;SER-GLN-GLU-PRO-PRO-ILE-SER-LEU-ASP-LEU-THR-PHE-HIS-LEU-LEU-ARG-GLU-VAL-LEU-GLU-MET-THR-LYS-ALA-ASP-GLN-LEU-ALA-GLN-GLN-ALA-HIS-SER-ASN-ARG-LYS-LEU-LEU-ASP-ILE-ALA-NH2 OVINE;corticotropin-releasinghormone;corticotropin-releasinghormone))-;CORTICOTROPIN RELEASING FACTOR SHEEP;CORTICOTROPIN RELEASING FACTOR, OVINE;CRF (OVINE)
• CAS NO: 9015-71-8
• Molecular Formula: C205H339N59O63S1
• Molecular Weight: 4670.31
• Product Categories: Peptide
• Mol File: 9015-71-8.mol
• Article Data: 0

Chemical Properties

• Appearance: /
• Storage Temp.: −20°C
• CAS DataBase Reference: CRF (OVINE)(CAS DataBase Reference)
• NIST Chemistry Reference: CRF (OVINE)(9015-71-8)
• EPA Substance Registry System: CRF (OVINE)(9015-71-8)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 9015-71-8(Hazardous Substances Data)

Usage

Description

CRF (Ovine), also known as Corticotropin-Releasing Hormone, is a peptide hormone that plays a crucial role in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis in response to internal or external stressors. It stimulates the secretion of adrenocorticotropic hormone (ACTH) from the pituitary gland, which in turn stimulates the adrenal cortex to produce cortisol and other stress-related hormones.

Uses

Used in Pharmaceutical Industry:
CRF (Ovine) is used as a research tool for studying the HPA axis and its role in stress response, as well as for the development of drugs targeting the HPA axis for the treatment of stress-related disorders.
Used in Diagnostic Applications:
CRF (Ovine) is used in diagnostic tests to evaluate the function of the HPA axis and to diagnose conditions such as Cushing's disease, Addison's disease, and other endocrine disorders.
Used in Veterinary Medicine:
CRF (Ovine) is used in veterinary medicine to assess the adrenal function in animals and to diagnose adrenal-related disorders in livestock.
Used in Neuroendocrine Research:
CRF (Ovine) is used in neuroendocrine research to study the interactions between the central nervous system and the endocrine system, as well as the role of CRF in the regulation of stress response and other physiological processes.

Discovery

The first evidence of a hypothalamic corticotropinreleasing substance was reported in 1955.The presence of a corticotropin-releasing hormone (CRH) was first reported in the ovine hypothalamus in 1981. Subsequently, CRH was found in the human, mouse, rat, pig, amphibian (Xenopus), teleost fish, cartilaginous fish, and lamprey. Novel members of the CRH family, CRH26,? and teleocortin (Tcn), have recently been reported in vertebrates (except teleosts and placental mammals) and the medaka, respectively.

Properties

Human/mouse/rat CRH: Mr 4758; pI 5.1. CRH peptides are freely soluble in water. The oxidation of methionine at position 21 remarkably decreases the activity of CRH.

Receptors

Three types of CRH receptors have been identified.? They belong to the family of seven-transmembrane-domain GPCRs and activate AC. Type-1 (CRHR1) and type-2 (CRHR2) receptors were identified in mammals, chicken, Xenopus, and teleosts. The type-3 receptor (CRHR3) was found in catfish. In mammals, the CRHR1 gene consists of 13 exons and 12 introns. The CRHR2 gene in humans consists of 12 exons and 11 introns, and three splice variants (CRHR2α, 2β, and 2γ) have been found; 2–12 exons are common to the three splice variants, and the first exon is specific for each variant. CRH binds to CRHR1 with high affinity. CRHR1 is mainly distributed in the anterior pituitary, and is involved in ACTH release. CRH also has high affinity to CRHR3. However, CRHR2 exhibits low affinity to CRH but high affinity to urotensin-I,sauvagine, and urocortins. CRHR2 is distributed in several restricted regions of the brain, but also in peripheral organs such as the heart, lung, muscle, and kidney. The CRH binding protein (CRH-BP, 37 kDa) has been highly conserved across evolution from crustaceans to humans. CRH-BP binds to CRH with high affinity and regulates CRH effects. In both mammals and nonmammalian vertebrates, pituitary and brain CRH-BP expression in the brain and pituitary are predominantly increased by stress. In the chicken, CRH2 is more potent in activating CRHR2 than CRHR1. In the medaka, Tcn and CRH have similar receptor interaction properties.

Signal transduction pathway

CRH activates AC via Gs protein-coupled with CRHRs. AC stimulates cAMP production, and cAMP, in turn, activates PKA, which phosphorylates downstream of cytosolic and nuclear targets such as CREB, resulting in induced gene transcription. Moreover, it is known that in addition to signaling pathways activated by cAMP, CRHR1 and CRHR2 trigger multiple signaling pathways such as the activation of p42/44 MAPK (ERK1/2).

Biological functions

CRH stimulates the synthesis and processing of proopiomelanocortin (POMC) to generate ACTH in the anterior pituitary. CRH also stimulates ACTH release. ACTH is secreted into the systemic circulation, reaches the adrenal cortex, and stimulates the synthesis and release of glucocorticoids. CRH also acts as a neuromodulator in the brain. CRH in the brain regulates the endocrine system, autonomic nervous system, and immune system in response to stress. In addition to the stress response, CRH is involved in multiple physiological functions such as suppression of food intake, regulation of body temperature, growth, metabolism, metamorphosis, reproduction, and diuresis. In mammals, CRH inhibits the female reproductive axis by suppressing gonadotropinreleasing hormone (GnRH) secretion. CRH2 stimulates TSHβ expression and shows a lower potency in inducing ACTH secretion in vitro in the chicken.

Synthesis and release

The synthesis and release of CRH are regulated by internal or external stress that is conveyed to the brain and is integrated at the hypothalamus, where CRH neurons exist. The synthesis and release of CRH are also regulated by diurnal rhythm and the negative feedback effect of cortisol. In nocturnal rats, CRH mRNA levels are higher at midday than at midnight. CRH is released from the axon terminal depending on Ca2+.

Clinical Use

Clinical implications Increased CRH production has been suggested to be associated with Alzheimer’s disease and depression. CRH deficiency has been observed to induce hypoglycemia and hepatitis. CRH has been used in the diagnosis of ACTH-dependent Cushing’s syndrome and Addison’s disease. Use for diagnosis and treatment CRHR1 antagonists Pexacerfont and Antalarmin are under clinical trial for the treatment of generalized anxiety disorder as well as depression and other mental disorders, respectively

Structure and conformation

CRH peptides of all species examined consist of 41 aa residues with an amidated C-terminus. The C-terminal region is important for physiological activity. The human, mouse, and rat CRH have identical aa sequences. CRH sequence homologies between human/mouse/rat and others are high (76%–95%). CRH2 peptides consist of 40–43 aa residues with an amidated C-terminus.