Regulatory Mechanisms of Corticotropin‐Releasing Hormone and Vasopressin Gene Expression in the Hypothalamus

Itoi, Keiichi; Jiang, Yaoguang; Iwasaki, Yusaku; Watson, Sally

doi:10.1111/j.0953-8194.2004.01172.x

Cited by 159 publications

(101 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Immunohistochemistry methods have been described previously (39 (40). Specifically, this technique has been used to quantify neuropeptides including OXT and AVP (41)(42)(43).…”

Section: Immunohistochemistrymentioning

confidence: 99%

Lack of cAMP-response Element-binding Protein 1 in the Hypothalamus Causes Obesity

Chiappini

Cunha

Harris

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

The melanocortin system in the hypothalamus controls food intake and energy expenditure. Its disruption causes severe obesity in mice and humans. cAMP-response element-binding protein 1 (CREB1) has been postulated to play an important role downstream of the melanocortin-4 receptor (MC4R), but this hypothesis has never been confirmed in vivo. To test this, we generated mice that lack CREB1 in SIM1-expressing neurons, of the paraventricular nucleus (PVN), which are known to be MC4R-positive. Interestingly, CREB1⌬SIM1 mice developed obesity as a result of decreased energy expenditure and impairment in maintaining their core body temperature and not because of hyperphagia, defining a new role for CREB1 in the PVN. In addition, the lack of CREB1 in the PVN caused a reduction in vasopressin expression but did not affect adrenal or thyroid function. Surprisingly, MC4R function tested pharmacologically was normal in CREB1 ⌬SIM1 mice, suggesting that CREB1 is not required for intact MC4R signaling. Thus CREB1 may affect other pathways that are implicated in the regulation of body weight.The melanocortin 4 receptor (MC4R) 2 is widely expressed in the central nervous system, including a number of sites that contribute to coordinated control of body weight (1-3). The essential role of the MC4R is evident from the presence of severe obesity in both MC4R knock-out mice and in humans with naturally occurring mutations (4, 5). These mutations cause increased food intake and decreased energy expenditure (4, 6, 7). One key site of MC4R expression is the paraventricular nucleus of the hypothalamus (PVN) (1-3). The PVN is an area that regulates several neuroendocrine, behavioral, and autonomic functions, especially food intake and energy expenditure (8 -11). It has been implicated in the regulation of body weight as re-expression of MC4R in the PVN of mice on a null background rescues the obese phenotype (12). Mutations in the SIM1 (single-minded 1) gene, a transcription factor that controls development of the PVN, lead to the development of obesity in humans and mice, further implicating the PVN as a key regulator of body weight (13-17).The MC4R is known to signal through G s ␣, which in turn activates adenylyl cyclase, leading to increased intracellular levels of cAMP (1, 3, 18). Elevated cAMP levels induce phosphorylation and activation of the transcription factor cAMP-response element-binding protein (CREB1) through increased activity of protein kinase A, or PKA (19 -22). The importance of this pathway in body weight regulation in vivo is highlighted by the fact that constitutive activation of PKA is associated with leanness (23). The phosphorylation of CREB1 leads to the activation of CREB target gene expression (24,25). CREB signaling is complicated by the fact that a number of related transcription factors including cAMP-response element modulator (CREM) and activating transcription factor 1 are also phosphorylated by PKA and can compensate for CREB1 in its absence. Although activating transcription factor 1 is not thought t...

show abstract

“…Immunohistochemistry methods have been described previously (39 (40). Specifically, this technique has been used to quantify neuropeptides including OXT and AVP (41)(42)(43).…”

Section: Immunohistochemistrymentioning

confidence: 99%

Lack of cAMP-response Element-binding Protein 1 in the Hypothalamus Causes Obesity

Chiappini

Cunha

Harris

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…The hallmark of the HPA axis response is a rapid increase in the release of hypothalamic corticotropin releasing factor (CRF) into the portal circulation and enhanced CRF transcription in the hypothalamic paraventricular nucleus (PVN), with the consequent increases in anterior pituitary ACTH and adrenocortical glucocorticoid secretion. In addition to their actions on systemic adaptation to stress, glucocorticoids exert a negative feedback control on CRF expression and release, limiting the HPA response in time and extent (Itoi et al, 2004). Such a complex and finely tuned response involves multiple neural pathways and loci of action.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II AT1 receptor blockade prevents the hypothalamic corticotropin-releasing factor response to isolation stress

et al. 2007

View full text Add to dashboard Cite

Sustained pretreatment with Angiotensin II AT 1 receptor antagonists prevents the sympathoadrenal and hormonal responses to 24 hour isolation stress. To elucidate the mechanism of the anti-stress effects of AT 1 receptor antagonism, we examined the effect of subcutaneous infusion of candesartan, a non-competitive AT 1 receptor antagonist, 0.5 mg/kg/day for 14 days, to Wistar rats on the hypothalamic pituitary adrenal (HPA) axis after 24 hour isolation stress. In the morning of day 15, we measured AT 1 receptors corticotropin releasing factor (CRF) mRNA and immunoreactive CRF in the paraventricular nucleus (PVN), the pituitary adrenocorticotropin hormone (ACTH) and adrenal corticosterone content, and the urinary corticosterone excretion. In rats not treated with candesartan, 24 hour isolation stress increased pituitary ACTH, adrenal corticosterone content and AT 1 receptor binding in the PVN but decreased CRF mRNA and CRF content in the PVN. This indicates enhanced CRF utilization not compensated by CRF gene transcription and effective glucocorticoid feedback inhibition in spite of the increase in AT 1 receptor expression. The effects of stress on HPA axis activation and CRF mRNA and content in the PVN were prevented by candesartan pretreatment, suggesting that activation of AT 1 receptors is required for the HPA axis response to isolation. Our results support the hypothesis that the activity of PVN AT 1 receptors is part of the mechanism necessary for development of a full stress-induced HPA axis activation. Inhibition of central AT 1 receptors limits the CRF response to stress and should be considered as a therapeutic tool to preserve homeostasis under chronic stress conditions.

show abstract

“…(22) Arginine vasopressin (AVP), is released following different stimuli, such as hypotension, hypoxia, hyperosmolarity, acidosis, and infection. (23) It has vasoconstrictor and antidiuretic properties, as well as the capacity to restore vascular tone in vasodilatory hypotension. Copeptin is a AVP precursor and its concentration mirrors that of AVP, both being elevated in sepsis and septic shock.…”

Section: Discussionmentioning

confidence: 99%

Comparação da acurácia de preditores de mortalidade na pneumonia associada à ventilação mecânica

Seligman

Teixeira

2011

J. bras. pneumol.

View full text Add to dashboard Cite

Objective: Levels of procalcitonin, midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal provasopressin (copeptin), and C-reactive protein (CRP), as well as Sequential Organ Failure Assessment (SOFA) scores, are associated with severity and described as predictors of outcome in ventilator-associated pneumonia (VAP). This study sought to compare the predictive value of these biomarkers for mortality in VAP. Methods: An observational study of 71 patients with VAP. Levels of procalcitonin, MR-proANP, copeptin, and CRP, together with SOFA scores, were determined at VAP onset, designated day 0 (D0), and on day 4 of treatment (D4). Patients received empirical antimicrobial therapy, with modifications based on culture results. Patients who died before D28 were classified as nonsurvivors. Results: Of the 71 patients evaluated, 45 were classified as survivors. Of the 45 survivors, 35 (77.8%) received appropriate antimicrobial therapy, compared with 18 (69.2%) of the 26 nonsurvivors (p = 0.57). On D0 and D4, the levels of all biomarkers (except CRP), as well as SOFA scores, were lower in eventual survivors than in eventual nonsurvivors. For D0 and D4, the area under the ROC curve was largest for procalcitonin. On D0, MR-proANP had the highest positive likelihood ratio (2.71) and positive predictive value (0.60), but procalcitonin had the highest negative predictive value (0.87). On D4, procalcitonin had the highest positive likelihood ratio (3.46), the highest positive predictive value (0.66), and the highest negative predictive value (0.93). Conclusions: The biomarkers procalcitonin, MR-proANP, and copeptin can predict mortality in VAP, as can the SOFA score. Procalcitonin alone has the greatest predictive power for such mortality.Keywords: Pneumonia, ventilator-associated/mortality; Biological markers/analysis; Health Status Indicators. ResumoObjetivo: Níveis de procalcitonina, midregional pro-atrial natriuretic peptide (MR-proANP, pró-peptídeo natriurético atrial midregional),, C-terminal provasopressin (copeptina), proteína C reativa (CRP) e escore do Sequential Organ Failure Assessment (SOFA) são associados a gravidade e descritos como preditores de desfechos na pneumonia associada a ventilação mecânica (PAVM). Este estudo procurou comparar o valor preditivo de mortalidade desses biomarcadores na PAVM. Métodos: Estudo observacional com 71 pacientes com PAVM. Níveis de procalcitonina, MR-proANP, copeptina e PCR, bem como escore de SOFA foram obtidos no dia do diagnóstico de PAVM, designado dia zero (D0), e no quarto dia de tratamento (D4) Os pacientes receberam tratamento antimicrobiano empírico, com modificações baseadas nos resultados de cultura. Os pacientes que morreram antes de D28 foram classificados como não sobreviventes. Resultados: Dos 71 pacientes, 45 sobreviveram. Dos 45 sobreviventes, 35 (77,8%) receberam tratamento antimicrobiano adequado, comparados com 18 (69,2%) dos 26 não sobreviventes (p = 0,57). Os sobreviventes apresentaram valores significativamente mais baixos em todos os b...

show abstract

Regulatory Mechanisms of Corticotropin‐Releasing Hormone and Vasopressin Gene Expression in the Hypothalamus

Cited by 159 publications

References 61 publications

Lack of cAMP-response Element-binding Protein 1 in the Hypothalamus Causes Obesity

Lack of cAMP-response Element-binding Protein 1 in the Hypothalamus Causes Obesity

Angiotensin II AT1 receptor blockade prevents the hypothalamic corticotropin-releasing factor response to isolation stress

Comparação da acurácia de preditores de mortalidade na pneumonia associada à ventilação mecânica

Contact Info

Product

Resources

About