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Naveen Kumar Thakral, Robert J Behme, Aktham Aburub, Jeffrey A Peterson, Timothy A Woods, Benjamin A Diseroad, Raj Suryanarayanan, Gregory A Stephenson
Disproportionation propensity of salts (HCl, HBr, hemi-napadisylate) and adipic acid co-crystal of corticotropin releasing hormone receptor-1 antagonist, was studied using model free kinetics. Using thermogravimetic weight loss profile or heat flow curves from differential scanning calorimetry, an activation energy plot for salts and co-crystal was generated based on model free kinetics. This activation energy of disproportionation provided qualitative information about the solid state salt stability. To ensure the stability throughout the shelf life, "prototype" formulations of salts and co-crystal in tablet form, were stored at 40 °C and several water vapor pressures...
October 21, 2016: Molecular Pharmaceutics
Chun Yeh, Ching-Heng Ting, Ming-Luen Doong, Chin-Wen Chi, Shou-Dong Lee, Chih-Yen Chen
PURPOSE: Urocortin 3 is a key neuromodulator in the regulation of stress, anxiety, food intake, gut motility, and energy homeostasis, while ghrelin elicits feeding behavior and enhances gastric emptying, adiposity, and positive energy balance. However, the interplays between urocortin 3 and ghrelin on food intake and gastric emptying remain uninvestigated. METHODS: We examined the differential effects of central O-n-octanoylated ghrelin, des-Gln(14)-ghrelin, and urocortin 3 on food intake, as well as on charcoal nonnutrient semiliquid gastric emptying in conscious rats that were chronically implanted with intracerebroventricular (ICV) catheters...
2016: Drug Design, Development and Therapy
Chulin Yu, Meiling Li, Yue Wang, Ying Liu, Chengzhi Yan, Jirong Pan, Jiali Liu, Sheng Cui
The corticotropin-releasing hormone (CRH) signaling system is involved in numbers of stress-related physiological and pathological responses,including its inhibiting effects on estradiol (E2) synthesis and follicular development in the ovary. In addition, there are reports that microRNAs (miRNAs) can control the function of animal reproductive system. The aim of present study was to investigate the functions of miR-375 and the relationship between miR-375 and CRH signaling molecules in the porcine ovary. First, our common PCR results show that miR-375 and the CRH receptor 1 (CRHR1) are expressed in porcine ovary, whereas CRH receptor 2 (CRHR2) is not detected...
October 18, 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
Anna P Pilbrow, Kathy A Lewis, Marilyn H Perrin, Wendy E Sweet, Christine S Moravec, W H Wilson Tang, Mark O Huising, Richard W Troughton, Vicky A Cameron
Corticotropin-releasing factor (CRF) and the CRF-related peptides, urocortin (Ucn)1, Ucn2 and Ucn3 signal through receptors CRFR1 and CRFR2 to restore homeostasis in response to stress. The Ucns exert potent cardioprotective effects and may have clinical utility in heart failure. To explore the activity of this system in the heart, we measured levels of myocardial gene expression of the CRF/Ucn family of ligands/receptors and investigated genetic variation and alternative splicing of CRFR1 in 110 heart failure patients and 108 heart donors...
October 18, 2016: Endocrinology
D A Bangasser, H Dong, J Carroll, Z Plona, H Ding, L Rodriguez, C McKennan, J G Csernansky, S H Seeholzer, R J Valentino
Several neuropsychiatric and neurodegenerative disorders share stress as a risk factor and are more prevalent in women than in men. Corticotropin-releasing factor (CRF) orchestrates the stress response, and excessive CRF is thought to contribute to the pathophysiology of these diseases. We previously found that the CRF1 receptor (CRF1) is sex biased whereby coupling to its GTP-binding protein, Gs, is greater in females, whereas β-arrestin-2 coupling is greater in males. This study used a phosphoproteomic approach in CRF-overexpressing (CRF-OE) mice to test the proof of principle that when CRF is in excess, sex-biased CRF1 coupling translates into divergent cell signaling that is expressed as different brain phosphoprotein profiles...
October 18, 2016: Molecular Psychiatry
Hyoseung Shin, Soon-Jin Choi, A-Ri Cho, Dong Young Kim, Kyu Han Kim, Ohsang Kwon
BACKGROUND: Stress is a known cause of hair loss in many species. OBJECTIVE: In this study, we investigated the role of acute stress on hair growth using a rat model. METHODS: Rats were immobilized for 24 hours and blood samples, and skin biopsies were taken. The effect of stress-serum on the in vitro proliferation of rat and human dermal papilla cells (hDPCs), as well as serum cortisol and corticotropin-releasing hormone levels, were measured...
October 2016: Annals of Dermatology
Ryota Tokunaga, Rie Shimoju, Hideshi Shibata, Mieko Kurosawa
Noxious cutaneous stimulation increases, whereas innocuous cutaneous stimulation decreases serotonin (5-HT) release in the central nucleus of the amygdala (CeA) in anesthetized rats. In the present study, we investigated the contribution of corticotropin releasing factor (CRF) receptors and gamma-aminobutyric acid (GABA) receptors in the dorsal raphe nucleus (DRN) to those responses. Release of 5-HT in the CeA was monitored by microdialysis before and after 10-min stimulation by pinching or stroking. Increased 5-HT release in the CeA in response to pinching was abolished by CRF2 receptor antagonism in the DRN...
October 15, 2016: Journal of Physiological Sciences: JPS
Ai-Ling Chen, Xi Sun, Wei Wang, Jin-Feng Liu, Xin Zeng, Jing-Fan Qiu, Xin-Jian Liu, Yong Wang
BACKGROUND: Immunosuppression has been described as a consequence of brain injury and infection by different mechanisms. Angiostrongylus cantonensis can cause injury to the central nervous system and eosinophilic meningitis to human. Both T cell and B cell immunity play an essential role in the resistance of the infection. However, whether brain injury caused by A. cantonensis infection can lead to immunosuppression is not clear. Therefore, the present study sought to observe the alteration of immune responses in mice infected with A...
October 12, 2016: Journal of Neuroinflammation
Jeff Sanders, Charles Nemeroff
The major neuropsychiatric disorders are devastating illnesses that are only modestly responsive to treatment. Improving the treatment of these conditions will require innovative new strategies that depart from previously focused-on pharmacological mechanisms. Considerable preclinical and clinical data indicate corticotropin-releasing factor (CRF) signaling as a target for new psychotropic drug development. Here we review alterations in the CRF system reported in several psychiatric conditions. We also examine the preclinical work that has dissected the distinctive roles of CRF receptors in specific circuits relevant to these disorders...
October 4, 2016: Trends in Pharmacological Sciences
Roshan R Naik, Trynke R de Jong
Motherhood brings about a multitude of behavioral and physiological changes in dams and some of these persist until after weaning. We studied behavioral changes associated with reproductive experience at lactating day (LD)8, at weaning (LD21), and 28 days post-weaning (PW28) compared to nulliparous (NP) females. Furthermore, in another cohort of animals, we quantified mRNA expression of five target genes known to be associated with maternal experience: arginin-vasopressin(Avp) and its 1A receptor(Avpr1a), oxytocin(Oxt) and its receptor(Oxtr), and corticotropin-releasing hormone(Crh) in three key maternal region: the medial preoptic area (MPOA), bed nucleus of the stria terminalis (BNST) and paraventricular hypothalamic nucleus(PVN)...
September 26, 2016: European Journal of Neuroscience
Cezary Skobowiat, Arnold E Postlethwaite, Andrzej T Slominski
The back skin of C57BL/6 mice was exposed to a single 400 mJ/cm(2) dose of ultraviolet B (UVB), and parameters of hypothalamic-pituitary-adrenal (HPA) axis in relation to immune activity were tested after 30-90 min following irradiation. Levels of brain and/or plasma corticotropin releasing hormone (CRH), β-endorphin, ACTH and corticosterone (CORT) were enhanced by UVB. Hypophysectomy had no effect on UVB-induced increases of CORT. Mitogen induced IFNγ production by splenocytes from UVB-treated mice was inhibited at 30, 90 min and after 24 h...
September 26, 2016: Photochemistry and Photobiology
P Schüssler, M Kluge, W Gamringer, T C Wetter, A Yassouridis, M Uhr, R Rupprecht, A Steiger
We reported previously that repetitive intravenous injections of corticotropin-releasing hormone (CRH) around sleep onset prompt depression-like changes in certain sleep and endocrine activity parameters (e.g. decrease of slow-wave sleep during the second half of the night, blunted growth hormone peak, elevated cortisol concentration during the first half of the night). Furthermore a sexual dimorphism of the sleep-endocrine effects of the hormones growth hormone-releasing hormone and ghrelin was observed. In the present placebo-controlled study we investigated the effect of pulsatile administration of 4×50μg CRH on sleep electroencephalogram (EEG) and nocturnal cortisol and GH concentration in young healthy women...
September 28, 2016: Psychoneuroendocrinology
Mei Hua Gao, Dimosthenis Giamouridis, N Chin Lai, Evelyn Walenta, Vivian Almeida Paschoal, Young Chul Kim, Atsushi Miyanohara, Tracy Guo, Min Liao, Li Liu, Zhen Tan, Theodore P Ciaraldi, Simon Schenk, Aditi Bhargava, Da Young Oh, H Kirk Hammond
Using mice rendered insulin resistant with high fat diets (HFD), we examined blood glucose levels and insulin resistance after i.v. delivery of an adeno-associated virus type 8 encoding murine urocortin 2 (AAV8.UCn2). A single i.v. injection of AAV8.UCn2-normalized blood glucose and glucose disposal within weeks, an effect that lasted for months. Hyperinsulinemic-euglycemic clamps showed reduced plasma insulin, increased glucose disposal rates, and increased insulin sensitivity following UCn2 gene transfer...
September 22, 2016: JCI Insight
Hossein Tezval, Natalia Dubrowinskaja, Inga Peters, Christel Reese, Katrin Serth, Faranaz Atschekzei, Jörg Hennenlotter, Arnulf Stenzl, Markus A Kuczyk, Jürgen Serth
The relevance of Corticotropin Releasing Hormone (CRH)-system in human malignancies is a question of growing interest. Here we investigated hypermethylation and epigenetic silencing of the CRH-Binding Protein (CRHBP) gene in clear cell renal cell cancer (ccRCC). Relative methylation of the CRHBP CpG island (CGI) was determined in 17 tumor cell lines as well as 86 ccRCC samples and 66 paired normal tissues using pyrosequencing and quantitative methylation specific PCR of bisulfite converted DNA. Results were statistically compared with relative mRNA expression levels of CRHBP and clinicopathological parameters of patients...
2016: PloS One
Zsolt Bagosi, Miklós Palotai, Balázs Simon, Péter Bokor, András Buzás, Beáta Balangó, Dávid Pintér, Miklós Jászberényi, Krisztina Csabafi, Gyula Szabó
The aim of the present study was to investigate the effects of the selective agonists of the corticotropin-releasing factor (CRF) 2 receptor, urocortin 2 (UCN 2) and urocortin 3 (UCN 3), on the anxiety- and depression-like signs induced by acute nicotine withdrawal in mice. In order to do so, male CFLP mice were exposed for 7 days to repeated intraperitoneal (IP) injection with nicotine or saline solution and 1day of acute withdrawal and then a single intracerebroventricular (ICV) injection with UCN 2, UCN 3 or saline solution...
September 29, 2016: Brain Research
Tomoyuki Kaneko, Katsuyuki Kaneda, Atsushi Ohno, Daiki Takahashi, Taiki Hara, Taiju Amano, Soichiro Ide, Mitsuhiro Yoshioka, Masabumi Minami
Pain is a complex experience involving sensory and affective components. Although the neuronal mechanisms underlying the sensory component of pain have been extensively studied, those underlying its affective component have yet to be elucidated. Recently, we reported that corticotrophin-releasing factor (CRF)-induced depolarization in type II neurons within the dorsolateral bed nucleus of the stria terminalis (dlBNST) is critical for pain-induced aversive responses in rats. However, the intracellular signaling underlying the excitatory effects of CRF and the contribution of such signaling to the induction of pain-induced aversion remain unclear...
September 30, 2016: European Journal of Neuroscience
Betty R McConn, Justin Matias, Guoqing Wang, Mark A Cline, Elizabeth R Gilbert
OBJECTIVE: The objective was to determine the effects of high-protein and high-fat diets, and fasting and refeeding, on appetite regulation in chicks. METHODS: Day of hatch chicks were fed one of four diets: basal, high protein (25% crude protein), and 15 and 30% high fat (15 and 30% metabolizable energy derived from soybean oil, respectively), and assigned to one of three treatments at 4 days: (1) access to feed, (2) 3 hours of fasting, or (3) fasting followed by 1 hour of refeeding...
August 16, 2016: Nutritional Neuroscience
Xin Zhang, Yuanbing Wu, Jin Hao, Jieyao Zhu, Ni Tang, Jinwen Qi, Shuyao Wang, Hong Wang, Shuang Peng, Ju Liu, Yundi Gao, Defang Chen, Zhiqiong Li
Urocortin-3 (UCN3), one of the corticotropin releasing factor (CRF) family peptides, which was discovered in 2001, has a variety of biological functions. However, the researches of UCN3 in fish were scarce. In order to understand whether UCN3 play a role in regulating food intake in fish, we first cloned the ucn3 cDNAs sequence of Siberian sturgeon (Acipenser baerii Brandt), and investigated the ucn3 mRNA levels in 11 tissues. The Siberian sturgeon ucn3 cDNA sequence was 1044bp, including an open reading frame (ORF) of 447bp that encoded 148 amino acids with a mature peptide of 40 amino acids, a 5'-terminal untranslated region (5'-UTR) of 162bp and a 3'-terminal untranslated region (3'-UTR) of 435bp...
September 22, 2016: Peptides
O G Shaker, S M R Eltahlawi, S O Tawfic, A M Eltawdy, N I E Bedair
BACKGROUND: Vitiligo is a disorder characterized by depigmented patches in the skin. Psychological stress can activate the hypothalamic-pituitary-adrenal axis in the brain as well as on the peripheral level and aggravate autoimmune skin diseases. Skin appendages have dual functions dually as prominent targets and sources of the peripheral corticotropin-releasing hormone (CRH)-proopiomelanocortin axis. AIM: To assess the role of CRH and CRHR-1 in vitiligo, and its possible association with psychological stress...
October 2016: Clinical and Experimental Dermatology
Xun Helen Hou, Minsuk Hyun, Julian Taranda, Kee Wui Huang, Emmalee Todd, Danielle Feng, Emily Atwater, Donyell Croney, Mark Lawrence Zeidel, Pavel Osten, Bernardo Luis Sabatini
Urine release (micturition) serves an essential physiological function as well as a critical role in social communication in many animals. Here, we show a combined effect of olfaction and social hierarchy on micturition patterns in adult male mice, confirming the existence of a micturition control center that integrates pro- and anti-micturition cues. Furthermore, we demonstrate that a cluster of neurons expressing corticotropin-releasing hormone (Crh) in the pontine micturition center (PMC) is electrophysiologically distinct from their Crh-negative neighbors and sends glutamatergic projections to the spinal cord...
September 22, 2016: Cell
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