Disease relevance of Crh

• The results also suggest that brain CRF has dual effects on food intake, hyperphagia and anorexia, in a stress-dependent manner [1].
• When adult obese rats were intracerebroventricularly-treated with ovine corticotropin-releasing hormone (oCRF) for 7 days, they stopped gaining body weight relative to vehicle-infused obese controls [2].
• The response of plasma ACTH to hypoglycemia was partially inhibited by the administration of CRF-antiserum (CRF-As) or AVP-antiserum (AVP-As) alone, but was found to be completely abolished by the administration of CRF-As + AVP-As as compared to the response in normal rabbit serum-treated rats [3].
• Elevated corticosterone and inhibition of ACTH responses to CRH and ether in the neonatal rat: effect of hypoxia from birth [4].
• It is proposed that: 1) hypothalamic NPY may play a role in the establishment and maintenance of the genetic obesity syndrome of the fa/fa rat, and 2) maintenance of the genetic obesity syndrome of the fa/fa rat, and 2) hypothalamic NPY could be partly regulated by central CRF [2].

Psychiatry related information on Crh

• Early life stress changes concentrations of neuropeptide Y and corticotropin-releasing hormone in adult rat brain. Lithium treatment modifies these changes [5].
• Changes in hypothalamic corticotropin-releasing hormone, neuropeptide Y, and proopiomelanocortin gene expression during chronic rapid eye movement sleep deprivation of rats [6].
• NMU did not induce locomotor activity in CRH knockout mice [7].
• Substantial data implicates hyperactivity of CRF neuronal systems in the pathophysiology of depression and anxiety disorders [8].
• The results show that injection of TRH into the NAS, but not the injection of LHRH or CRH, selectively increases face grooming without affecting other subcategories of grooming at the doses used, and appears to link this peptide with the neural substrate of stereotyped behavior [9].

High impact information on Crh

• Synthetic urocortin evokes secretion of adrenocorticotropic hormone (ACTH) both in vitro and in vivo and binds and activates transfected type-1 CRF receptors, the subtype expressed by pituitary corticotropes [10].
• We have characterized another mammalian member of the CRF family and have localized its urotensin-like immunoreactivity to, and cloned related complementary DNAs from, a discrete rat midbrain region [10].
• Although it has been demonstrated that vasopressin and CRF are present in the same neurosecretory granules of EZ fibres, parallel determinations of vasopressin and CRF in pituitary portal blood have shown alterations of the concentration of vasopressin without a concomitant change in that of CRF [11].
• Such a dissociation suggests that either differential release of vasopressin and CRF can occur from a single population of nerve endings, or there are fibres in the pituitary-stalk ME which release vasopressin but not CRF [11].
• The discrete anatomical distribution of arginine vasopressin and corticotropin releasing factor (CRF) immunoreactivity in the paraventricular nucleus (PVN) of the rat hypothalamus is altered after adrenalectomy [12].

Chemical compound and disease context of Crh

• The present study examined the effect of local administration of the CRF antagonist, alpha-helical CRF9-41, or peripheral treatment with dexamethasone on NPY-induced hyperphagia [13].
• In contrast, the levels of corticotropin-releasing hormone (CRH) and vasopressin (VP) mRNAs in the hypothalamic paraventricular nucleus (PVN) as well as of VP mRNA in the supraoptic nucleus (SON) were unaffected by maternal undernutrition [14].
• These studies examined the expression of CRF in the urinary bladder and lumbosacral sacral parasympathetic nucleus (SPN) in response to cyclophosphamide (CYP)-induced cystitis (4 h, 48 h, or chronic) in rats [15].
• These findings demonstrate that acute cholestasis in the rat is associated with suppression of hypothalamic-pituitary-adrenal axis responsiveness to stress and demonstrate a dissociation between mechanisms of ACTH regulation mediated by CRF and AVP [16].
• Hypotensive hemorrhage elevates corticotropin-releasing hormone messenger ribonucleic acid (mRNA) but not vasopressin mRNA in the rat hypothalamus [17].

Biological context of Crh

• Long-term antidepressant administration alters corticotropin-releasing hormone, tyrosine hydroxylase, and mineralocorticoid receptor gene expression in rat brain. Therapeutic implications [18].
• This elevation of blood pressure was markedly inhibited by CRH (5 microgram) [19].
• We investigated the effect of CRH in a number of animal models by using i.v. Evans blue extravasation as a marker of vascular permeability [20].
• We hypothesize that the effects are mediated by rapid, direct vasodilation induced by CRH that decreases baroreceptor input to the brain stem, leading to a rapid release of AVP that induces the antidiuresis by direct action on the V(2)Rs in the kidney [19].
• Within the first hour, CRH caused antidiuresis, antinatriuresis, and antikaliuresis together with reduction in urinary cGMP output that, in the fourth hour, were replaced by diuresis, natriuresis, and kaliuresis accompanied by increased cGMP output [19].

Anatomical context of Crh

• In the light of data that major depression is associated with an activation of brain CRH and LC-NE systems, the time-dependent effect of long-term imipramine administration on decreasing the gene expression of CRH in the hypothalamus and TH in the LC may be relevant to the therapeutic efficacy of this agent in depression [18].
• These findings suggest that CRH induces skin vascular permeability through NT acting on mast cells and that both peptides should be considered in the pathogenesis of skin disorders exacerbated by stress [20].
• However, HR rats exhibited higher levels of CRH mRNA in the hypothalamic paraventricular nucleus but lower basal levels in the central nucleus of the amygdala [21].
• Moreover, B or T MPOA implants also decreased resting-state levels of AVP but not CRH in the median eminence, and these effects were correlated with ACTH responses to restraint [22].
• The stress-induced increases in mRNA levels of CRH in the PVN and TH in the locus coeruleus were reduced by imipramine but not by Hypericum [23].

Associations of Crh with chemical compounds

• Corticotropin-releasing hormone causes antidiuresis and antinatriuresis by stimulating vasopressin and inhibiting atrial natriuretic peptide release in male rats [19].
• Opposite effects of DEX on CRH secretion were observed in cultures consisting of PVN cells only [24].
• The functional viability of these ARC/PVN cultures was verified by their ability to synthesize and secrete CRH, AVP, and beta-END under basal and depolarizing (veratridine) conditions in vitro [24].
• It is generally accepted that CRF stimulates activation of adenylate cyclase, whereas AVP activates phosphoinositidase in pituitary corticotropes [25].
• These effects were mediated by the CRH type 1 receptor because its antagonist antalarmin blocked CRH-induced apoptosis and Fas ligand expression [26].

Physical interactions of Crh

• The actions of CRF are mediated by G-protein coupled membrane bound receptors and a high affinity CRF receptor, CRF1, has been previously cloned and functionally characterized [27].
• Corticotropin-releasing factor type 1 and type 2alpha receptors regulate phosphorylation of calcium/cyclic adenosine 3',5'-monophosphate response element-binding protein and activation of p42/p44 mitogen-activated protein kinase [28].
• NMU that interacts anatomically and/or functionally with the CRH system is a novel physiological regulator of stress response [7].
• During atrial pulsation, a stimulus mimicking volume loading and associated with a reduction of systemic ACTH levels, we observed a significant decline in portal concentrations of immunoreactive AVP coupled with a nonsignificant trend toward reduced portal immunoreactive CRF levels [29].
• CRF microinjected into the dorsal vagal complex inhibits TRH analog- and kainic acid-stimulated gastric contractility in rats [30].

Co-localisations of Crh

• The BDNF mRNA signal belatedly co-localizes with CRH and AVP mRNA signals in the PVN, as determined by in situ hybridization [31].
• Cell counts of double-labeled neurons in the paraventricular nucleus of the hypothalamus (PVH) demonstrated that glucocorticoid receptor-like-IR is colocalized in virtually all the CRF and vasopressin immunoreactive parvocellular neurons studied, which respond to adrenalectomy by increased peptide expression [32].

Regulatory relationships of Crh

• CRH induced Fas ligand production and apoptosis [26].
• Intracerebroventricular BDNF injections (5 microg/rat) in non-anesthetized adult male rats induce a gradual increase in the CRH mRNA signal whereas AVP mRNA signal progressively decreases in the parvocellular and magnocellular PVN portions [31].
• However, whether hypothalamic CRF levels influence changes in hippocampal GR expression (and memory function), via reduced CRF receptor activation and consequent lower plasma glucocorticoid levels, is unclear [33].
• These studies demonstrated changes in the expression of CRF in urinary bladder and SPN region with CYP-induced cystitis and CRF receptor (CRF(2)) expression in nerve fibers and urothelium in control rats [15].
• Double label staining was also performed to determine if NPY Y1 receptors were expressed in CRH neurons [34].

Other interactions of Crh

• The deduced protein encodes a peptide that we name urocortin, which is related to urotensin (63% sequence identity) and CRF (45% sequence identity) [10].
• This heterogeneous distribution of CRF1 and CRF2 receptor mRNA suggests distinctive functional roles for each receptor in CRF-related systems [27].
• These results strongly suggest that BDNF could be a stress-responsive intercellular messenger since when it is exogenously administered acts as an important and early component in the activation and recruitment of hypothalamic CRH and AVP neurons [31].
• This study investigated the effect of CRF on NPY release in vivo, measured by push-pull techniques, in the anesthetized rat [35].
• Hippocampal GR and hypothalamic CRF mRNA levels and stress-induced plasma corticosterone levels were also examined [33].

Analytical, diagnostic and therapeutic context of Crh

• Exposure of ARC/PVN cocultures to the glucocorticoid dexamethasone (DEX) resulted in a dose-dependent increase of CRH secretion and an inhibition of AVP and beta-END; the CRH responses deviated strikingly from predictions based on in vivo experiments [24].
• Adrenalectomy (ADX) leads to a decrease in the number of CRF-binding sites in the rat anterior pituitary (AP) [36].
• Acute immobilization caused a significant increase in CRH, but not AVP, mRNA levels in the parvocellular PVN in sham rats [37].
• The mRNA level was determined by Northern blot analysis using a rat brain CRF-R1 complementary RNA probe [36].
• When CRF was administered into the PVN via the push-pull cannula at 1 or 5 microg/ml, dose-dependent increases in NPY overflow of two- and fivefold were observed (p < 0.05) [35].

References