Pharmacology and Biology of Corticotropin-Releasing Factor (CRF) Receptors

Eckart, Klaus; Jahn, Olaf; Radulović, Jelena; Radulović, Marko; Blank, Thomas; Stiedl, Oliver; Brauns, Olaf; Tezval, Hossein; Zeyda, Thomas; Spiess, Joachim

doi:10.3109/10606820213678

Cited by 23 publications

(38 citation statements)

References 114 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Some brain regions exhibit a decline in CRHr1 and r2 expression as the animal matures, whereas other regions show increased gene expression during specific stages of development (Avishai-Eliner et al, 1996;Eghbal-Ahmadi et al, 1998). To our knowledge, the expression of CRH binding protein early in development has not been described (Eckart et al, 2002) and the modulation of these CRH-related molecules by stress has been relatively unexplored during development. Therefore, we hypothesized that maternal deprivation would alter the ontogenic progression of CRH, CRHbp and CRHr1 and that a differential modulation would be observed in deprived vs. non-deprived animals dependent on the glucocorticoid rise observed when exposed to the relative moderate stressor of restraint.…”

Section: Introductionmentioning

confidence: 99%

Brain corticotropin-releasing hormone (CRH) circuits in the developing rat: Effect of maternal deprivation

et al. 2006

View full text Add to dashboard Cite

Early in life, there is a delicate and critical balance aimed to maintain low hormone responses derived from the stress responsive hypothalamic-pituitary-adrenal axis (HPA). However, in the infant rat hypothalamic corticotrophin-releasing hormone (CRH) stress responses to environmental events are clearly seen even though other elements of the HPA axis may have limited responses. In view of the role of CRH in mediating behavior associated with stress and anxiety, we considered the ontogeny and the effects of prolonged maternal deprivation (DEP) in brain areas that express CRH-related molecules outside the hypothalamus. We hypothesized that DEP would alter the ontogeny of CRH, CRH binding protein and CRH receptor 1 in prefrontal cortex, amygdala, septum and hippocampus, areas that are part of the CRH extra hypothalamic system, and that a differential modulation would be observed in response to restraint. We compared non-deprived animals to animals subjected to 24 h of DEP at 6, 12 and 18 days of life. We found (1) developmental patterns, which were idiosyncratic to the anatomical area examined, and (2) a temporal response of mRNA levels which was also site specific. The genomic changes are not always related to maternal deprivation status, in fact DEP enhanced, suppressed or had no consequence on the underlying ontogenic progression and restraint response of these CRH-related molecules. We conclude that the extra hypothalamic CRH system is a dynamic system responding to developmental and environmental demands challenging the basic assumption of stress hypo responsiveness in the infant rat. This modulation may have important repercussions on morphological organization and events leading to neuroprotection.

show abstract

Section: Introductionmentioning

confidence: 99%

Brain corticotropin-releasing hormone (CRH) circuits in the developing rat: Effect of maternal deprivation

et al. 2006

View full text Add to dashboard Cite

show abstract

“…In the case of normal human epidermal keratinocytes, the lack of CRH/ urocortin-induced production of cAMP (22) together with lack of effect of PKA inhibitors on CRH induced keratinocyte differentiation program (23) indicates poor coupling of CRHR1alpha to G s in these cells. In SKMEL-188 melanoma cells, which only express the CRHR1d isoform, the lack of coupling to cAMP with overt stimulation of Ca 2+ flux suggests that the CRH-R1d signal transduction pathway is only coupled to either voltage-activated Ca 2+ ion channels or PLC (12,15,22,25,39 (6,16,40). Indeed, we found that CRH does stimulate CREB DNA binding activity in HaCaT cells (Figure 4), although this was not seen in normal adult epidermal keratinocytes.…”

Section: Second Messengersmentioning

confidence: 99%

“…In humans the gene coding for CRH-R1 generate at least 7 alternatively spliced CRH-R1 transcripts (1,2,6,15,16); it contains 14 exons with exon 6 being unique in that it is only present in CRH-R1beta (that contains all 14 exons). In the main functional isoform, CRH-R1alpha, exon 6 is spliced out; in other isoforms there are additional splicing sites, for example, CRHR1c (exon 3 is spliced out), CRH-R1d (exons 13 is absent), CRH-R1e (exons 3, 4 are absent, which cause frame shift and early stop codon in exon 8), CRH-R1f (exon 12 is absent resulting in frame shift), CRH-R1g (exons 11, 27 bp of exon 10 and 28 bp of exon 12 are absent), and CRH-R1h (insertion of cryptic exon between exons 4 and 5 cause frame shift and early termination codon in exon 5).…”

Section: Alternatively Spliced Crh-rs Isoforms: An Overviewmentioning

confidence: 99%

See 1 more Smart Citation

Corticotropin releasing hormone and the skin

Słomiński¹

2006

Front Biosci

139

228

View full text Add to dashboard Cite

Cotricotropin-releasing hormone (CRH) and related peptides are produced in skin that is dependent on species and anatomical location. Local peptide production is regulated by ultraviolet radiation (UVR), glucocorticoids and phase of the hair cycle. The skin also expresses the corresponding receptors (CRH-R1 and CRH-R2), with CRH-R1 being the major receptor in humans. CRH-R1 is expressed in epidermal and dermal compartments, and CRH-R2 predominantly in dermal structures. The gene coding for CRH-R1 generates multiple isoforms through a process modulated by UVR, cyclic adenosine monophosphate (cAMP) and phorbol 12-myristate 13-acetate. The phenotypic effects of CRH in human skin cells are largely mediated by CRH-R1alpha through increases in concentrations of cAMP, inositol triphosphate (IP 3 ), or Ca 2+ with subsequent activation of protein kinases A (PKA) and C (PKC) dependent pathways. CRH also modulates the activity of nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-kappaB), activator protein 1 (AP-1) and cAMP responsive element binding protein (CREB). The cellular functions affected by CRH depend on cell type and nutritional status and include modulation of differentiation program(s), proliferation, viability and immune activity. The accumulated evidence indicates that cutaneous CRH is also a component of a local structure organized similarly to the hypothalamo-pituitary-adrenal axis. KeywordsHuman Skin; Hormone; Corticotropin; CRH; CRH-R1; CRH-R2; Urocortin; Review INTRODUCTIONCRH is the central trigger of HPA axis, and together with related peptides urocortin I-III also regulate behavioral, autonomic, endocrine, reproductive, cardiovascular, gastro-intestinal, metabolic and immune systemic functions (1-11). Other actions include local immunomodulatory (predominantly proinflammatory) effects (12)(13)(14), differing from a central immunosuppressive activity (through the HPA axis) (3). Of note, locally produced CRH can directly regulate steroid hormone production by adrenals and gonads (1,2). Furthermore, CRH in the immune cells can induce production and release of proopiomelanocortin (POMC) derived adrenocorticotropin (ACTH) and beta-endorphin peptides. NIH Public Access Author ManuscriptFront Biosci. Author manuscript; available in PMC 2007 April 2. Published in final edited form as:Front Biosci. ; 11: 2230-2248. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptIn vertebrates these peptides interact with membrane-bound CRH-R1 and CRH-R2 (1,2). Both receptor types belong to the group II subfamily of G protein-coupled receptors (GPCRs). CRH-R1 binds CRH and urocortin I with high affinity; it does not bind urocortin II (strescopin related protein). CRH-R2 shows preferential affinity for urocortin II, although it also binds CRH, however, with lower affinity than CRH-R1. Signal transduction through CRH-Rs is coupled to the activation of adenylate cyclase (AC), phospholipase C (PLC) and calcium channels (1, 2,5,6). ALTERNATIVELY SPLICED CRH-RS ISOFORMS: AN OVER...

show abstract

“…Its modulation of serotonin and norepinephrine release specifically supports a role in emotional responding as these neurotransmitter systems are implicated in affective and anxiety responses (both normal and disordered) (Charney, 2004;Koob, 1999). Hence, CRF is well situated to modulate circuits involved in cognition, defensive behavior and emotion.CRF acts via at least 2 known G-protein-coupled receptors, CRF 1 and CRF 2 (Chang et al, 1993;Chen et al, 1993;Liaw et al, 1996;Lovenberg et al, 1995;Perrin et al, 1993; for a review, see Eckart et al, 2002 andDautzenberg andHauger, 2002). In rodents, both receptors are expressed in relatively discrete nuclei of the neocortex, amygdala and extended amygdala (bed nucleus stria terminalis), nucleus accumbens, hypothalamus, pituitary and sensory relay nuclei (Van Pett et al, 2000).…”

mentioning

confidence: 99%

Role of corticotropin releasing factor in anxiety disorders: A translational research perspective

Risbrough

Stein

2006

Hormones and Behavior

211

139

View full text Add to dashboard Cite

Anxiety disorders are a group of mental disorders that include generalized anxiety disorder (GAD), panic disorder, phobic disorders (e.g., specific phobias, agoraphobia, social phobia) and posttraumatic stress disorder (PTSD). Anxiety disorders are among the most common of all mental disorders and, when coupled with an awareness of the disability and reduced quality of life they convey, they must be recognized as a serious public health problem. Over 20 years of preclinical studies point to a role for the CRF system in anxiety and stress responses. Clinical studies have supported a model of CRF dysfunction in depression and more recently a potential contribution to specific anxiety disorders (i.e., panic disorder and PTSD). Much work remains in both the clinical and preclinical fields to inform models of CRF function and its contribution to anxiety. First, we will review the current findings of CRF and HPA axis abnormalities in anxiety disorders. Second, we will discuss startle reflex measures as a tool for translational research to determine the role of the CRF system in development and maintenance of clinical anxiety. KeywordsCRH; CRF; Posttraumatic stress disorder; Anxiety; Panic disorder; Startle Overview of CRF neuroendocrine effects and its effects on G-protein-coupled receptorsCorticotropin releasing factor (CRF; also termed "CRH" for corticotropin releasing hormone) was first described in Science by Vale et al. (1981). They reported the discovery of a hypothesized hypothalamic factor, CRF, a 41 amino acid peptide which selectively and potently activated pituitary corticotropin (or adrenal corticotropin releasing hormone, ACTH) secretion. They predicted that this peptide could be "a key signal in mediating and integrating an organism's endocrine, visceral and behavioral response to stress" (Vale et al., 1981(Vale et al., p. 1397). More than 20 years of subsequent animal research and clinical studies have confirmed this hypothesis, supporting a role for CRF, and its more recently discovered ligand family Urocortin 1, 2 and 3, in anxiety and stress responses Reyes et al., 2001;Spina et al., 1996). In this review, we will focus on the current state of knowledge of CRF system dysregulation in clinical anxiety and discuss future avenues of translational research on the role of CRF in startle phenotypes observed in some anxiety disorders. CRF mediation of the neuroendocrine response to stressIn response to stress, CRF is released from the median eminence of the hypothalamus, where it subsequently binds to receptors at the anterior pituitary and increases ACTH release into the * Corresponding author. 8950 Villa La Jolla Drive, Suite B-218, La Jolla, CA 92037, USA. E-mail address: mstein@ucsd.edu (M.B. Stein). bloodstream. ACTH consequently acts at the adrenal cortex to facilitate release of glucocorticoids such as cortisol. This system, known as the hypothalamic-pituitary-adrenal axis (HPA), is an important component of the response to stress and has been shown to be dysregulated in both anxiety and de...

show abstract

Pharmacology and Biology of Corticotropin-Releasing Factor (CRF) Receptors

Cited by 23 publications

References 114 publications

Brain corticotropin-releasing hormone (CRH) circuits in the developing rat: Effect of maternal deprivation

Brain corticotropin-releasing hormone (CRH) circuits in the developing rat: Effect of maternal deprivation

Corticotropin releasing hormone and the skin

Role of corticotropin releasing factor in anxiety disorders: A translational research perspective

Contact Info

Product

Resources

About