scholarly journals Differential Increase in Forebrain and Caudal Neurosecretory System Corticotropin-Releasing Factor and Urotensin I Gene Expression Associated with Seawater Transfer in Rainbow Trout

Endocrinology ◽  
2005 ◽  
Vol 146 (9) ◽  
pp. 3851-3860 ◽  
Author(s):  
Paul M. Craig ◽  
Haider Al-Timimi ◽  
Nicholas J. Bernier

Abstract Transfer to seawater (SW) in rainbow trout elicits an increase in plasma cortisol and a bout of anorexia. Although the corticotropin-releasing factor (CRF) system has known hypophysiotropic and anorexigenic properties, it is not known whether CRF-related peptides originating from either the forebrain or the caudal neurosecretory system (CNSS) play a role during SW acclimation. Therefore, we examined the effects of SW transfer on food intake, plasma osmolality, hypothalamic-pituitary-interrenal axis activity, and the expression of CRF and urotensin I (UI) in the forebrain and the CNSS. While SW transfer chronically suppressed food intake over a 2-wk period, it transiently increased plasma osmolality, ACTH, and cortisol. Similarly, 24 h after SW transfer, hypothalamic and preoptic area CRF mRNA levels were significantly increased but recovered to pretransfer levels within 7 d. Conversely, SW transfer elicited a delayed increase in hypothalamic UI mRNA levels and had no effect on preoptic area UI expression. In the CNSS, SW exposure was associated with parallel increases in CRF and UI mRNA levels from 24 h post transfer through 7 d. Finally, in situ hybridization demonstrated an extensive and overlapping pattern of CNSS CRF and UI expression. These results differentially implicate specific neuronal populations of the CRF system in the acute and chronic responses to a hyperosmotic stress and suggest that forebrain and CNSS CRF-related peptides have different roles in the coordinated response to fluid balance disturbances.

2007 ◽  
Vol 196 (3) ◽  
pp. 637-648 ◽  
Author(s):  
Nicholas J Bernier ◽  
Sarah L Alderman ◽  
Erin N Bristow

Corticotropin-releasing factor (CRF)- and urotensin I (UI)-expressing cells of the preoptic area (POA) and caudal neurosecretory system (CNSS) are considered key contributors to the regulation of the stress response in fish; however, the expression pattern of these neurons to environmental and social challenges have not been compared in a single study. Therefore, we characterized in rainbow trout (Oncorhynchus mykiss) the central distribution of CRF and UI expression and quantified the POA and CNSS mRNA levels of both transcripts in response to hyperammonemia, hypoxia, isolation, or subordination. The tissue distribution demonstrated that the POA and the CNSS are dominant sites of CRF and UI expression. Comparison of the plasma cortisol levels in response to the diverse treatments showed that subordination was the most severe stressor followed by hyperammonemia, isolation, and hypoxia. In the POA, with the exception of subordination that had no effect on UI expression, all stressors resulted in increase in CRF and UI mRNA levels. In the CNSS, while hyperammonemia was associated with increase in CRF and UI mRNA levels, and hypoxia induced an increase in CRF expression, isolation caused a decrease in the expression of both transcripts, and subordination had no effect. Independent of the stressor, we found strong positive correlations between CRF and UI expression in the POA and the CNSS, and no correlation in the expression of either gene between regions. Overall, the results demonstrate that the contribution of POA and CNSS CRF and UI neurons to the stress response in rainbow trout is stressor-, time-, and region-specific.


2005 ◽  
Vol 289 (4) ◽  
pp. R982-R990 ◽  
Author(s):  
Nicholas J. Bernier ◽  
Paul M. Craig

Hypoxia stress suppresses appetite in a variety of fish species, but the mechanisms mediating this response are not known. Therefore, given their anorexigenic and hypophysiotropic properties, we investigated the contribution of forebrain corticotropin-releasing factor (CRF) and urotensin I (UI) to the regulation of food intake and the hypothalamic-pituitary-interrenal (HPI) stress axis in hypoxic rainbow trout. Exposure to 50 and 35% O2 saturation for 24 h decreased food intake by 28 and 48%, respectively. The 35% O2 treatment also increased forebrain CRF and UI mRNA levels, plasma cortisol, and lactate. Exposure for 72 h to the same conditions resulted in similar reductions in food intake, increases in plasma cortisol proportional to the hypoxia severity, and increases in forebrain CRF and UI mRNA levels in the 50% O2 treatment. Relative to saline-infused fish, chronic intracranial infusion of the CRF receptor antagonist α-helical CRF(9–41) reduced the appetite-suppressing effects of 24-h exposure to 35% O2 and blocked the hypoxia-induced increase in plasma cortisol. Finally, forebrain microdissection revealed that 50 and 35% O2 exposure for 24 h specifically increases preoptic area CRF and UI mRNA levels in proportion to the severity of the hypoxic challenge and either has no effect or elicits small decreases in other forebrain regions. These results show that CRF-related peptides play a physiological role in regulating the HPI axis and in mediating at least a portion of the reduction in food intake under hypoxic conditions in rainbow trout and demonstrate that the response of forebrain CRF and UI neurons to this stressor is region specific.


2005 ◽  
Vol 186 (1) ◽  
pp. 123-130 ◽  
Author(s):  
C Doyon ◽  
V L Trudeau ◽  
T W Moon

The objectives of this study were to characterize rainbow trout (Oncorhynchus mykiss) corticotropin-releasing factor (CRF)-binding protein (CRF-BP) cDNA and to examine the variations in CRF-BP and CRF mRNA levels in response to different intensities of stress. Trout were physically disturbed by a single or three consecutive periods of chasing until exhaustion followed by 2 h of recovery. The pituitary CRF-BP and preoptic area CRF1 mRNA contents were significantly increased only after repeated chasing events. Physical disturbance increased plasma cortisol levels with the largest change occurring in the group of trout that were exposed to repeated chasing events. Trout were also individually isolated in 120 l tanks or confined to 1.5 l boxes for 4, 24 or 72 h. CRF-BP mRNA levels in confined fish were greater than those of isolated fish at 72 h although there were no differences compared with the control group. CRF1 mRNA levels in the preoptic area were greater and remained elevated for a longer period in confined compared with isolated trout. Isolation led to a transient increase in plasma cortisol levels, but the higher cortisol values developed in the confined fish suggest that this treatment was more stressful than isolation. These results demonstrate that the intensity and duration of stress are important factors regulating CRF and CRF-BP mRNA levels in rainbow trout. We hypothesize that pituitary CRF-BP is involved in regulating the activity of the stress axis, possibly by reducing access to CRF1 receptors in the corticotropes.


1998 ◽  
Vol 83 (2) ◽  
pp. 448-452
Author(s):  
H. F. Erden ◽  
I. H. Zwain ◽  
H. Asakura ◽  
S. S. C. Yen

Recently, we reported that the thecal compartment of the human ovary contains a CRF system replete with gene expression and protein for corticotropin-releasing factor (CRF), CRF-Receptor 1 (CRF-R1), and the blood-derived high affinity CRF-binding protein (CRF-BP). Granulosa cells are devoid of the CRF system. The parallel increases in intensity of CRF, CRF-R1, and 17α-hydroxylase messenger ribonucleic acid (mRNA) and proteins in thecal cells with follicular maturation suggest that the intraovarian CRF system may play an autocrine role regulating androgen biosynthesis, with a downstream effect on estrogen production by granulosa cells. The functionality of the ovarian CRF system may be conditioned by the relative presence of plasma-derived CRF-BP by virtue of its localization of protein, but not transcript in thecal cells and its ability to compete with CRF for the CRF receptor. To further these findings, in the present study we have examined the effect of CRF on LH-stimulated 17α-hydroxylase (P450c17) gene expression and androgen production by isolated thecal cells from human ovarian follicles (11–13 mm). During the 48-h culture, addition of LH (10 ng/mL) to the medium increased by 5- and 6-fold dehydroepiandrosterone and androstenedione production by thecal cells. Remarkably, the LH-stimulated, but not basal, androgen production was inhibited by CRF in a time- and dose-dependent manner. The half-maximal (ID50) effect dose of CRF occurred at 5 × 10−8 mol/L, and at a maximal concentration of 10−6 mol/L, CRF completely inhibited LH-stimulated androgen production. This inhibitory effect of CRF became evident at 12 h (45%), and by 24 h the effect was more pronounced, with a 70% reduction from baseline. As determined by Northern analyses, CRF dose dependently decreased LH-stimulated P450c17 mRNA levels, with a maximal inhibition of 85% P450c17 gene expression at a CRF concentration of 10−6 mol/L. With the addition of 10−6 mol/L of the antagonist α-helical CRF-(9–41), the inhibitory effect of CRF was partially reversed for both P450c17 mRNA (75%) and androgen production (50%), indicating the CRF-R1-mediated event. In conclusion, the present study demonstrated a potent inhibitory effect of CRF on LH-stimulated dehydroepiandrosterone and androstenedione production that appears to be mediated through the reduction of P450c17 gene expression. Thus, the ovarian CRF system may function as autocrine regulators for androgen biosynthesis in the thecal cell compartment to maintain optimal substrate for estrogen biosynthesis by granulosa cells. Further studies to define the role of CRF-BP in the endocrine modulation of the intraovarian CRF system are needed.


2011 ◽  
Vol 107 (11) ◽  
pp. 1714-1725 ◽  
Author(s):  
A. Cláudia Figueiredo-Silva ◽  
Sadasivam Kaushik ◽  
Frédéric Terrier ◽  
Johan W. Schrama ◽  
Françoise Médale ◽  
...  

We examined the long-term effect of feeding coconut oil (CO; rich in lauric acid, C12) on voluntary food intake and nutrient utilisation in rainbow trout (Oncorhynchus mykiss), with particular attention to the metabolic use (storage or oxidation) of ingested medium-chain TAG. Trout were fed for 15 weeks one of the four isoproteic diets containing fish oil (FO) or CO as fat source (FS), incorporated at 5 % (low fat, LF) or 15 % (high fat, HF). Fat level or FS did not modify food intake (g/kg0·8per d), despite higher intestinal cholecystokinin-T mRNA in trout fed the HF-FO diet. The HF diets relative to the LF ones induced higher growth and adiposity, whereas the replacements of FO by CO resulted in similar growth and adiposity. This, together with the substantial retention of C12 (57 % of intake), suggests the relatively low oxidation of ingested C12. The down-regulation of carnitine palmitoyl-transferase-1 (CPT-1) confirms the minor dependency of medium-chain fatty acids (MCFA) on CPT-1 to enter the mitochondria. However, MCFA did not up-regulate mitochondrial oxidation evaluated using hepatic hydroxyacyl-CoA dehydrogenase as a marker, in line with their high retention in body lipids. At a low lipid level, MCFA increased mRNA levels of fatty acid synthase, elongase and stearoyl-CoA desaturase in liver, showing the hepatic activation of fatty acid synthesis pathways by MCFA, reflected by increased 16 : 0, 18 : 0, 16 : 1, 18 : 1 body levels. The high capacity of trout to incorporate and transform C12, rather than to readily oxidise C12, contrasts with data in mammals and may explain the absence of a satiating effect of CO in rainbow trout.


2015 ◽  
Vol 226 (2) ◽  
pp. 103-119 ◽  
Author(s):  
Barry N Madison ◽  
Sara Tavakoli ◽  
Sarah Kramer ◽  
Nicholas J Bernier

To gain a better understanding of the mechanisms by which cortisol suppresses growth during chronic stress in fish, we characterized the effects of chronic cortisol on food intake, mass gain, the expression of appetite-regulating factors, and the activity of the GH/IGF axis. Fish given osmotic pumps that maintained plasma cortisol levels at ∼70 or 116 ng/ml for 34 days were sampled 14, 28 and 42 days post-implantation. Relative to shams, the cortisol treatments reduced food intake by 40–60% and elicited marked increases in liver leptin (lep-a1) and brain preoptic area (POA) corticotropin-releasing factor (crf) mRNA levels. The cortisol treatments also elicited 40–80% reductions in mass gain associated with increases in pituitarygh, liverghreceptor (ghr), liverigfIandigfbinding protein (igfbp)-1 and -2 mRNA levels, reduced plasma GH and no change in plasma IGF1. During recovery, while plasma GH and pituitarygh, liverghrandigfIgene expression did not differ between treatments, the high cortisol-treated fish had lower plasma IGF1 and elevated liverigfbp1mRNA levels. Finally, the cortisol-treated fish had higher plasma glucose levels, reduced liver glycogen and lipid reserves, and muscle lipid content. Thus, our findings suggest that the growth-suppressing effects of chronic cortisol in rainbow trout result from reduced food intake mediated at least in part by increases in liverlep-a1and POAcrfmRNA, from sustained increases in hepaticigfbp1expression that reduce the growth-promoting actions of the GH/IGF axis, and from a mobilization of energy reserves.


2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 466-466
Author(s):  
Hossein Tezval ◽  
Axel S. Merseburger ◽  
Markus A. Kuczyk ◽  
Christoph von Klot ◽  
Juergen Serth

466 Background: Urocortin (Ucn), a 40 amino acid peptide, belongs to the corticotropin releasing factor (CRF) family and exerts its actions mainly in the periphery through activation of two CRF receptors (CRFRs), CRFR1 and CRFR2 and a binding protein (CRFBP/CRHBP). Both receptors are G-protein coupled and binding of Ucn leads to activation of cAMP-dependent protein kinases via elevation of cAMP levels. Ucn and Urocortin III (UcnIII) are involved in conditions such as regulation of local inflammation, angiogenesis, and inhibition of proliferation. Suppression of neovascularization and inhibition of tumor cell cycling by Urocortins is modulated through CRFRs. Activation of CRFRs by e.g. Ucn inhibits angiogenesis via reduction of vascular endothelial growth factor (VEGF) and suppresses the cell proliferation. Here we characterized the whole CRF family on mRNA levels quantitatively comparing the normal and clear cell carcinoma of the kidney (ccRCC). Methods: In this study we measured the mRNA level of Ucn, UcnIII, CRFR1, CRFR2 and CRHBP in 78 RCC samples and paired histologically normal appearing tissues using quantitative PCR. Statistical analyses were carried out using univariate logistic regression analysis. Results: We found tumour specific down regulation of mRNA expression of UcnIII, CRFR1, CRFR2 and CRHBP in samples of RCCs with clear cell histology compared to paired normal tissues (P<0.01 for all targets). Only Ucn did not show any expression difference between two groups (p=0.17). Conclusions: For the first time we showed the expression profile of the whole CRF peptide family in ccRCC compared to normal kidney on mRNA level. Our data underlines the malfunction of this actually strong protective and anticancer system in renal malignancy and shows the involvement of CRF system in carcinogenesis in kidney. More studies are necessary to find out the detailed roles of the CRF system in renal carcinoma.


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