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Corticotropin releasing (factor OR hormone)

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https://www.readbyqxmd.com/read/28103786/crh-receptor-signalling-potential-roles-in-pathophysiology
#1
Styliani Ourailidou, Dimitris Grammatopoulos
To maintain homeostatic equilibrium, living organisms have evolved complex adaptation systems that control an array of behavioural, autonomic, neuroendocrine and immune responses. One of the important switches The master switch of this system is the hypothalamic hormone corticotropin-releasing hormone (CRH), which together with a family of related peptides (urocortins, UCNs) orchestrate stress-coping responses that reinstate homeostasis. Persistent disturbances in the homeostatic equilibrium either due to inadequate or persistently uncontrolled responses have been associated with pathogenic mechanisms of disease...
January 10, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28103785/non-peptide-crf-receptor-antagonists-allosterism-kinetics-and-translation-to-efficacy-in-human-disease
#2
Dimitri E Grigoriadis, Samuel R J Hoare
G-Protein coupled receptors (GPCRs) have been, and remain a key target of drug discovery programs for human disease. While many drugs have been developed that interact with these proteins in the simple classic manner - that is - physically blocking the cognate ligand from simply binding to its target receptor, drug discovery approaches have elucidated alternative more complex methods by which small molecules can interact with these receptors and block their function. This is most evident in the Class B GPCRs where the cognate ligands are relatively large peptides with multiple points of contact on the GPCR spanning both hydrophilic and hydrophobic domains on the same protein to elicit function...
January 10, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28103784/the-multi-faceted-profile-of-corticotropin-releasing-factor-crf-family-of-neuropeptides-and-of-their-receptors-on-the-paracrine-local-regulation-of-the-inflammatory-response
#3
Andrew N Margioris, Eirini Dermitzaki, Maria Venihaki, Christos Tsatsani, Achille Gravanis, Pavlina Avgoustinaki, George Liapakis
The corticotropin releasing factor (CRF) family of neuropeptides, CRF and the Urocortins, and their receptors are present not only within the central nervous system but also in the periphery at various locations and at the sites of inflammation where they influence its progress in a complex local / paracrine manner. These neuropeptides are either produced locally, by components of the inflammatory response or they may reach the inflammation sites via postganglionic sympathetic and sensory afferent nerve transport...
January 9, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28103783/understanding-corticotropin-releasing-factor-receptor-crfr-activation-using-structural-models
#4
Arnau Cordomi, George Liapakis, Minos Timotheos Matsoukas
The corticotropin-releasing factor type 1 and 2 receptors (CRF1R and CRF2R) belong to the secretin-like family, also known as class B1, of G protein-coupled receptors (GPCRs). Several endogenous hormones mediate their responses through the CRF receptors, such as CRF and the urocortins. The structures for the N-terminus extracellular domain of both CRF1R and CRF2R in complex with peptidic ligands were released a few years ago and permitted the study of hormone binding to the orthosteric binding site. It was not until more recently, when the crystal structure of the transmembrane domain of human CRF1R in its inactive state bound to an allosteric antagonist became available...
January 10, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28103782/structures-of-the-first-extracellular-domain-of-crf-receptors
#5
Viviane Zelenay, Marilyn Perrin, Roland Riek
Corticotropin releasing factor (CRF) receptors belong to the secretin family of G protein-coupled receptors (GPCRs) and are responsible for initiating endocrine stress responses and mediating anxiety related behaviors upon activation via stressors. The main binding site for the CRF ligands is the first extracellular domain (ECD) of the receptors. Several structures of ligand-free and ligand-bound ECDs were recently determined either by nuclear magnetic resonance (NMR) spectroscopy or X-ray crystallography. They reveal how the ligands bind through both hydrophobic and hydrophilic interactions to the ECDs, which is highly dynamic in absence of ligands...
January 10, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28103781/prospective-clinical-applications-of-crf-peptide-antagonists
#6
Jean E Rivier
It is noteworthy that thirty three years of efforts in corticotropin releasing factor (CRF) research by academia and the pharmaceutical industry resulted in several thousand papers and patents, yet little progress has been made to identify and market diagnostic or therapeutic CRF peptides and small molecule ligands. We document the potential relevance of CRF peptide antagonists to reinvigorate stress/anxiety affected "anatomy systems" in order to boost their efficacy.
January 10, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28101317/corticotropin-releasing-factor-overexpression-in-mice-abrogates-sex-differences-in-body-weight-visceral-fat-and-food-intake-response-to-a-fast-and-alters-levels-of-feeding-regulatory-hormones
#7
Lixin Wang, Miriam Goebel-Stengel, Pu-Qing Yuan, Andreas Stengel, Yvette Taché
BACKGROUND: Corticotropin-releasing factor overexpressing (CRF-OE) male mice showed an inhibited feeding response to a fast, and lower plasma acyl ghrelin and Fos expression in the arcuate nucleus compared to wild-type (WT) mice. We investigated whether hormones and hypothalamic feeding signals are impaired in CRF-OE mice and the influence of sex. METHODS: Male and female CRF-OE mice and WT littermates (4-6 months old) fed ad libitum or overnight fasted were assessed for body, adrenal glands and perigonadal fat weights, food intake, plasma hormones, blood glucose, and mRNA hypothalamic signals...
2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/28096430/testing-hypotheses-about-individual-variation-in-plasma-corticosterone-in-free-living-salamanders
#8
Jessica R Thomas, Andrew J Magyan, Peter E Freeman, Sarah K Woodley
In vertebrates, many responses to stress as well as homeostatic maintenance of basal metabolism are regulated by plasma glucocorticoid hormones (GCs). Despite having crucial functions, levels of GCs are typically variable among individuals. We examined the contribution of several physiological factors to individual variation in plasma corticosterone (CORT) and the number of corticotropin-releasing hormone (CRH) neurons in the magnocellular preoptic area of the brain in free-living Allegheny Mountain dusky salamanders...
January 17, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28094875/neuroendocrinology-of-mast-cells-challenges-and-controversies
#9
REVIEW
Theoharis C Theoharides
Mast cells (MC) are hemopoietically-derived tissue immune cells that are ubiquitous in the body, including neuroendocrine organs such as the hypothalamus, pineal, pituitary, ovaries, pancreas and uterus where their action is not well understood. Mast cells have historically been associated with allergies because of their rich content of histamine and tryptase, but more recently with regulation of immunity and inflammation due their synthesis and release of numerous cytokines and chemokines. Mast cells are located perivascularly and express numerous receptors for diverse ligands such as allergens, pathogens, neurotransmitters, neuropeptides and hormones including acetylcholine, calcitonin gene-related peptide (CGRP), corticosteroids, corticotropin-releasing hormone (CRH), β-endorphin, epinephrine, 17β-estradiol, gonadotrophins, hemokinin-A (HKA), leptin, melatonin, neurotensin (NT), parathyroid hormone (PTH), substance P (SP) and vasoactive instestinal peptide (VIP)...
January 17, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28094761/homeodomain-protein-otp-affects-developmental-neuropeptide-switching-in-oxytocin-neurons-associated-with-a-long-term-effect-on-social-behavior
#10
Einav Wircer, Janna Blechman, Nataliya Borodovsky, Michael Tsoory, Ana Rita Nunes, Rui F Oliveira, Gil Levkowitz
Proper response to stress and social stimuli depends on orchestrated development of hypothalamic neuronal circuits. Here we address the effects of the developmental transcription factor orthopedia (Otp) on hypothalamic development and function. We show that developmental mutations in the zebrafish paralogous gene otpa but not otpb affect both stress response and social preference. These behavioral phenotypes were associated with developmental alterations in oxytocinergic (OXT) neurons. Thus, otpa and otpb differentially regulate neuropeptide switching in a newly identified subset of OXT neurons that co-express the corticotropin-releasing hormone (CRH)...
January 17, 2017: ELife
https://www.readbyqxmd.com/read/28094283/adolescent-chronic-stress-and-adult-anxiety-adolescent-chronic-unpredictable-stress-exposure-is-a-sensitive-window-for-long-term-changes-in-adult-behavior-in-mice
#11
Nicole L Yohn, Julie A Blendy
Adolescence is a time period in development when the brain undergoes substantial remodeling in response to the environment. To determine if a stressful experience during adolescence affects adult behavior, we exposed adolescent male and female C57BL/6J mice to chronic unpredictable stress (CUS) for 12 days starting at post-natal day 28 (PND28). We also exposed adult male and female mice to CUS for 12 days beginning at PND70 to determine if adolescence is a sensitive time period when stress can have long-lasting effects on behavior...
January 17, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28090002/easy-detection-of-hormone-secretion-from-l%C3%AE-t2-cells-by-using-gaussia-luciferase
#12
Kazuhiro Satou, Yuta Mochimaru, Takashi Nakakura, Tomoyuki Kusada, Jun Negishi, Shiori Musha, Nanaka Yoshimura, Yukio Kato, Hideaki Tomura
Reproduction is regulated by gonadotropins secreted from gonadotrophs. The production and secretion of gonadotropins are mainly regulated by gonadotropin-releasing hormone (GnRH). Agonists or antagonists that influence GnRH action on gonadotrophs are important to regulate reproduction; however, these factors have not been fully characterized due to the lack of simple and easy-to-use techniques to detect gonadotropin secretion from gonadotropin-producing cells. In the present study, we found that Gaussia luciferase (Gluc), which was expressed in LβT2 cells, can be secreted like a luteinizing-hormone (LH) upon stimulation with GnRH...
January 15, 2017: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/28089702/the-visible-burrow-system-a-view-from-across-the-hall
#13
REVIEW
James P Herman, Kellie L Tamashiro
The visible burrow system (VBS) is an ethologically relevant social stress model that creates a distinct dominance hierarchy in rats. Randall Sakai's laboratory performed an impressive series of studies documenting the very different impact of VBS exposure on the brain and behavior of dominants (DOM) and subordinates (SUBs). Hierarchy formation causes pronounced changes in metabolism in SUBs relative to both DOMs and unstressed controls, resulting in marked weight loss and metabolic imbalance. Stress testing revealed multiple phenotypes in the VBS, including DOMs, stress-responsive SUBs and stress-non-responsive SUBs...
January 12, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28089628/crf1-but-not-glucocorticoid-receptor-antagonists-reduce-separation-induced-distress-vocalizations-in-guinea-pig-pups-and-crf-overexpressing-mouse-pups-a-combination-study-with-paroxetine
#14
P Monika Verdouw, Joantine C J van Esterik, Bernard W M M Peeters, Mark J Millan, Lucianne Groenink
RATIONALE: Given the large number of patients that does not respond sufficiently to currently available treatment for anxiety disorders, there is a need for improved treatment. OBJECTIVES: We evaluated the anxiolytic effects of corticotropin releasing factor (CRF)1 receptor antagonists and glucocorticoid receptor (GR) antagonists in the separation-induced vocalization test in guinea pigs and transgenic mice with central CRF overexpression. Furthermore, we explored effects of these drugs when given in combination with a suboptimal dose of a selective serotonin re-uptake inhibitor (SSRI)...
January 12, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28071586/milestones-in-crh-research
#15
George P Chrousos, Emmanouil Zoumakis
The Corticotropin-releasing Hormone (CRH) mammalian family members include CRH, urocortin I, Stresscopin (SCP) and Stresscopin-related peptide (SRP), along with the CRH receptors type 1 (CRHR1) and type 2 (CRHR2), and CRH-binding protein (CRH-BP). These family members differ in their tissue distribution and pharmacology. Several studies have provided evidence supporting an important role of this family in the regulation of the neuroendocrine and behavioral responses to stress. Regulation of the relative contribution of CRH and its homologs and the two CRH receptors in brain CRH pathways may be essential in coordinating physiologic responses to stress...
January 9, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28057867/molecular-diversity-of-corticotropin-releasing-hormone-mrna-containing-neurons-in-the-hypothalamus
#16
Roman A Romanov, Alan Alpar, Tomas Hökfelt, Tibor Harkany
Hormonal responses to acute stress rely on the rapid induction of corticotropin-releasing hormone (CRH) production in the mammalian hypothalamus, with subsequent instructive steps culminating in corticosterone release at the periphery. Hypothalamic CRH neurons in the paraventricular nucleus of the hypothalamus are therefore considered "stress neurons". However, significant morphological and funtional diversity amongst neurons that can transiently produce CRH in other hypothalamic nuclei has been proposed, particularly since histochemical evidence associates CRH to both GABA and glutamate neurotransmission...
January 5, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28057851/corticotropin-releasing-hormone-improves-survival-in-pneumococcal-pneumonia-by-reducing-pulmonary-inflammation
#17
Brittney Burnley, Harlan P Jones
The use of glucocorticoids to reduce inflammatory responses is largely based on the knowledge of the physiological action of the endogenous glucocorticoid, cortisol. Corticotropin-releasing hormone (CRH) is a neuropeptide released from the hypothalamic-pituitary-adrenal axis of the central nervous system. This hormone serves as an important mediator of adaptive physiological responses to stress. In addition to its role in inducing downstream cortisol release that in turn regulates immune suppression, CRH has also been found to mediate inflammatory responses in peripheral tissues...
January 2017: Physiological Reports
https://www.readbyqxmd.com/read/28052282/changes-in-intestinal-motility-and-gut-microbiota-composition-in-a-rat-stress-model
#18
Takaaki Murakami, Kazuhiro Kamada, Katsura Mizushima, Yasuki Higashimura, Kazuhiro Katada, Kazuhiko Uchiyama, Osamu Handa, Tomohisa Takagi, Yuji Naito, Yoshito Itoh
BACKGROUND: Irritable bowel syndrome (IBS) causes chronic abdominal pain and abnormal bowel movements. The etiology involves complicated interactions among visceral hypersensitivity, disorders related to bowel movements, and stress. Changes in the microbiota affect the IBS pathophysiology. We investigated changes in colorectal motility, structure, and microbiota in response to stress due to maternal separation (MS) and corticotropin-releasing hormone (CRH) administration in rats. SUMMARY: Neonatal rats were separated from their mothers for 3 h daily from postnatal day (PND) 2 to PND14...
2017: Digestion
https://www.readbyqxmd.com/read/28050629/antireward-compulsivity-and-addiction-seminal-contributions-of-dr-athina-markou-to-motivational-dysregulation-in-addiction
#19
REVIEW
George F Koob
RATIONALE AND OBJECTIVES: Addiction is defined as a chronically relapsing disorder characterized by compulsive drug seeking that is hypothesized to derive from multiple sources of motivational dysregulation. METHODS AND RESULTS: Dr. Athina Markou made seminal contributions to our understanding of the neurobiology of addiction with her studies on the dysregulation of reward function using animal models with construct validity. Repeated overstimulation of the reward systems with drugs of abuse decreases reward function, characterized by brain stimulation reward and presumbably reflecting dysphoria-like states...
January 3, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28028605/neuropeptide-systems-and-new-treatments-for-nicotine-addiction
#20
REVIEW
Adriaan W Bruijnzeel
RATIONALE: The mildly euphoric and cognitive enhancing effects of nicotine play a role in the initiation of smoking, while dysphoria and anxiety associated with smoking cessation contribute to relapse. After the acute withdrawal phase, smoking cues, a few cigarettes (i.e., lapse), and stressors can cause relapse. Human and animal studies have shown that neuropeptides play a critical role in nicotine addiction. OBJECTIVES: The goal of this paper is to describe the role of neuropeptide systems in the initiation of nicotine intake, nicotine withdrawal, and the reinstatement of extinguished nicotine seeking...
December 28, 2016: Psychopharmacology
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