Regulatory Mechanisms Underlying Corticotropin-Releasing Factor Gene Expression in the Hypothalam

Kageyama, Kazunori; Suda, Toshio

doi:10.1507/endocrj.k09e-075

Cited by 90 publications

(63 citation statements)

References 60 publications

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“…Activation of this pathway leads to the binding of CREB to the CRE on the CRF promoter [6] . We also previously found that pituitary adenylate cyclase-activating polypeptide stimulates CRF promoter activity via the PKA pathway in hypothalamic cells [15,22] . In hypothalamic cells, forskolin-stimulated CRF gene transcription was mediated by a functional CRE, which included -220 to -233 bp on the CRF 5 -promoter region [23] .…”

Section: Discussionmentioning

confidence: 72%

Cytokines Induce NF-ĸB, Nurr1 and Corticotropin-Releasing Factor Gene Transcription in Hypothalamic 4B Cells

Kageyama

Kagaya²,

Takayasu³

et al. 2010

Neuroimmunomodulation

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Objective: In the hypothalamus, corticotropin-releasing factor (CRF) plays a central role in regulating stress responses. Cytokines are important mediators of the interaction between the neuroendocrine and immune systems, and are implicated in the regulation of CRF expression. Following inflammatory challenges, interleukin (IL)-1 or IL-6 stimulates the hypothalamic-pituitary-adrenal axis. CRF promoter contains multiple nuclear factor (NF)-ĸB and Nurr1 binding sites. In the present study, we determined the ability of the signaling pathways to activate the CRF gene in the hypothalamic paraventricular nucleus following inflammatory challenge. Methods: Cytokine-induced changes in CRF gene expression were examined in the hypothalamic system. Luciferase assay and Western blotting were performed to assess transcriptional activity and the nuclear translocation of transcriptional factors. Results: IL-1β, IL-6 and tumor necrosis factor (TNF)-α stimulated the nuclear expression levels of NF-ĸB, NF-ĸB-dependent Nurr1 and c-Fos proteins. Direct stimulatory effects of TNF-α and IL-1β, in addition to IL-6, were found on the transcriptional activity of the CRF gene in hypothalamic 4B cells. Conclusion: These cytokines are involved in the regulation of CRF gene activity in hypothalamic cells.

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Section: Discussionmentioning

confidence: 72%

Cytokines Induce NF-ĸB, Nurr1 and Corticotropin-Releasing Factor Gene Transcription in Hypothalamic 4B Cells

Kageyama

Kagaya²,

Takayasu³

et al. 2010

Neuroimmunomodulation

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“…Although several reports on the effect of E 2 on the HPA axis performed in cell cultures and animal models (rats, sheep) are available (McCormick et al 1998;Ochedalski et al 2007;Ogura et al 2008;Kageyama and Suda 2009;Weiser and Handa 2009;Handa and Weiser 2014;van Lier et al 2014), the mechanisms have not yet been fully elucidated. In general, it has been proposed that E 2 could exert a stimulatory effect on the hypothalamus, the corticotroph cells or the adrenal gland cortex (by stimulating CRH secretion or inhibiting glucocorticoid feedback, or stimulating ACTH synthesis or cortisol synthesis/secretion) (Burgess and Handa 1993;Carey et al 1995;McCormick et al 1998;Lo et al 2000;van Lier et al 2003b;Ochedalski et al 2007; Kageyama and Suda 2009;Weiser and Handa 2009;Handa and Weiser 2014;Panagiotakopoulos and Neigh 2014).…”

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confidence: 99%

“…In general, it has been proposed that E 2 could exert a stimulatory effect on the hypothalamus, the corticotroph cells or the adrenal gland cortex (by stimulating CRH secretion or inhibiting glucocorticoid feedback, or stimulating ACTH synthesis or cortisol synthesis/secretion) (Burgess and Handa 1993;Carey et al 1995;McCormick et al 1998;Lo et al 2000;van Lier et al 2003b;Ochedalski et al 2007; Kageyama and Suda 2009;Weiser and Handa 2009;Handa and Weiser 2014;Panagiotakopoulos and Neigh 2014).…”

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confidence: 99%

Plasma ACTH, α-MSH and cortisol variations in the dog during the oestrous cycle in different photoperiods

Gallelli¹,

Monachesi²,

Miceli³

et al. 2015

Vet. Med. - Czech

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ABSTRACT:The hypothalamic-pituitary-adrenal axis (HPA) is a complex system regulated by multiple factors. Sexual dimorphism of this axis has been described in different species under physiological conditions and it has been proposed that sexual hormones could have an effect on it. There are only a few reports about sex-linked variations in HPA axis hormones in the dog. Thus, studying the impact of sexual hormones on the HPA axis would broaden the knowledge about its function in this species. Therefore, the objective of this study was to determine whether there are variations in HPA plasma hormones (ACTH, alfa-melanocyte-stimulating hormone [α-MSH] and cortisol) according to the sex and photoperiod (positive or negative photoperiod were considered when the duration of the light hours of the day was more than 12 or less than 12, respectively) under basal conditions (like anoestrus) and throughout the oestrous cycle in the female dog. The population under study consisted of 11 intact female and 14 intact male dogs. Under basal conditions neither ACTH nor α-MSH concentrations showed differences between sexes and different photoperiods. Cortisol showed greater values in the negative photoperiod than in the positive, both in females and males (P = 0.03 and P = 0.015, respectively). Throughout the oestrous cycle, all the studied hormones showed variations (P < 0.0001). The greatest concentrations of ACTH were observed at proestrus, while α-MSH and cortisol showed their greatest concentrations at oestrus. The three hormones decreased in diestrus. ACTH and cortisol concentrations were higher in the negative photoperiod (P = 0.04 and P < 0.0001, respectively), while α-MSH concentrations were higher in the positive photoperiod (P = 0.012). In the group of females oestradiol and progesterone correlated with ACTH (r = 0.75, P < 0.0001; r = 0.34, P < 0.01, respectively), α-MSH (r = 0.49, P < 0.0001; r = 0.52, P < 0.0001, respectively) and cortisol (r = 0.33, P < 0.01; r = 0.5, P < 0.0001, respectively). These results show that in females, HPA axis hormones vary during the oestrous cycle in relation to oestradiol and progesterone fluctuations. The ACTH, α-MSH and cortisol concentrations also showed differences between photoperiods in females, but only cortisol did so in males. These findings suggest that sexual hormones could have an effect on the HPA axis. Further research needs to be done to fully understand this interaction and the mechanisms involved.

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“…At the pituitary level, peak C. salmositica infection was associated with a significant increase in crf-r1 gene expression. Although increases in crf-r1 gene expression are observed after the application of an acute stressor in mammals, chronic CRF stimulation of pituitary CRF-R1 leads to a down-regulation of crf-r1 mRNA expression (Rabadan-Diehl et al 1996, Kageyama & Suda 2009). Similarly, 24 h of chronic restraint stress in common carp concomitantly increases the gene expression of POA crf and reduces the gene expression of pituitary crf-r1 (Huising et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Duress without stress: Cryptobia infection results in HPI axis dysfunction in rainbow trout

Madison¹,

Woo²,

Bernier³

2013

Journal of Endocrinology

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Despite clear physiological duress, rainbow trout (Oncorhynchus mykiss) infected with the pathogenic haemoflagellate Cryptobia salmositica do not appear to mount a cortisol stress response. Therefore, we hypothesized that the infection suppresses the stress response by inhibiting the key effectors of the hypothalamic-pituitary-interrenal (HPI) axis. To test this, we characterized the basal activity of the HPI axis and the cortisol response to air exposure in saline-and parasite-injected fish. All fish were sampled at 4 and 6 weeks post-injection (wpi). While both the treatment groups had resting plasma cortisol levels, the parasite-infected fish had lower levels of plasma ACTH than the control fish. Relative to the control fish, the infected fish had higher mRNA levels of brain pre-optic area corticotrophin-releasing factor (CRF) and pituitary CRF receptor type 1, no change in pituitary POMC-A1, -A2 and -B gene expression, higher and lower head kidney melanocortin 2 receptor mRNA levels at 4 and 6 wpi respectively and reduced gene expression of key proteins regulating interrenal steroidogenesis: StAR, cytochrome P450scc and 11b-hydroxylase. The parasite-infected fish also had a reduced plasma cortisol response to a 60-s air exposure stressor. Superfusion of the head kidney tissues of the parasite-infected fish led to significantly lower ACTH-stimulated cortisol release rates than that observed in the control fish. These novel findings show that infection of rainbow trout with C. salmositica results in complex changes in the transcriptional activity of both central and peripheral regulators of the HPI axis and in a reduction in the interrenal capacity to synthesize cortisol.

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Regulatory Mechanisms Underlying Corticotropin-Releasing Factor Gene Expression in the Hypothalam

Cited by 90 publications

References 60 publications

Cytokines Induce NF-ĸB, Nurr1 and Corticotropin-Releasing Factor Gene Transcription in Hypothalamic 4B Cells

Cytokines Induce NF-ĸB, Nurr1 and Corticotropin-Releasing Factor Gene Transcription in Hypothalamic 4B Cells

Plasma ACTH, α-MSH and cortisol variations in the dog during the oestrous cycle in different photoperiods

Duress without stress: Cryptobia infection results in HPI axis dysfunction in rainbow trout

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