Expression of Corticotropin-Releasing Hormone Type 1 Receptor in Paraventricular Nucleus after Acute Stress

Abstract

We have previously proposed the existence of ultrashort loop-positive feedback regulation of corticotropin-releasing hormone (CRH) in the hypothalamus. To gain a better understanding of this effect, we performed double-label in situ hybridization to identify the neurons in the paraventricular nucleus (PVN) that express CRH type 1 receptor (CRH-R1) following stress. We also conducted immunohistochemistry to determine whether CRH-R1 mRNA was translated to CRH-R1 protein in the PVN. Thirty-minute restraint stress given to male Wistar rats increased c-fos mRNA expression primarily in the CRH-producing neurons of the parvocellular PVN. Small numbers of vasopressin and oxytoxin-producing cells were also labeled by c-fos probes. Approximately 70% of CRH-R1 positive neurons exhibited CRH mRNA 2 h after the beginning of stress, while only a small percentage of the vasopressin and oxytocin-producing cells coexpressed CRH-R1 mRNA. CRH-R1 immunoreactivity, which was detected in the perikarya and fibers of PVN neurons, appeared to increase in response to stress, though this was not statistically significant. Pretreatment with a selective CRH-R1 antagonist, CP-154,526, significantly attenuated stress-induced corticotropin (ACTH) secretion as well as c-fos mRNA expression in the PVN. These results demonstrate that acute stress increases neuronal activation and CRH-R1 mRNA expression primarily in CRH-producing neurons of the parvocellular PVN, that CRH-R1 message is translated to CRH-R1 protein, and that PVN neurons are activated at least in part through CRH-R1 under acute stress. The data further support the possibility of feedback regulation of CRH itself in CRH-producing neurons.

Increased interleukin-6 receptor expression in the paraventricular nucleus of rats with heart failure

“…In addition, consistent with CRF-mediated responses, Ucn I has been shown to stimulate ACTH release in healthy rats (63) and humans (12), as well as in sheep (49) and humans (11) with HF via binding to the CRF 1 receptor in the PVN. Although the influence of HF on endogenous Ucn-1 production is unknown, it is possible that Ucn-1 concomitantly with CRF may contribute to the neural-humoral activation characteristic of HF as the CRF 1 and CRF 2 receptor subtypes (11) for Ucn-1 and CRF are expressed in PVN tissue (26). Furthermore, Ucn-1 release is known to induce IL-6 expression in aortic smooth muscle cells (28).…”

Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances

“…Moreover, CRFR1 seems to be involved in the antidepressant response to selective serotonin reuptake blocker. 11 CRFR2, which opposes the actions of CRFR1 22 and mediates an anxiolytic effect, 50 showed nonsignificant change, indicating an imbalance in the regulation of CRF in depression via the two CRF receptors. Our data support the hypothesis that increased CRF signaling via CRFR1 is an important mechanism in the pathogenesis of depression and that CRFR1 antagonists might be an effective novel class of antidepressant drugs.…”

“…MR and GR can form hetero-and homodimers that differ in their activity of gene regulation. A change in the balance of MR/GR ratio in depressed patients may contribute to the change in transcription rate of CRF [16][17][18][19][20] ; (2) the CRF receptors, that is, CRFR1 that stimulates CRF production 21,22 and CRFR2 that opposes this action 23 ; (3) alterations in vasopressinergic systems that potentiate effects of CRF 24 and the AVP receptor 1a (AVPR1A) that is involved in anxiety/ depressionrelated behavior 25 ; oxytocin (OXT) that attenuates the stress response was found to be increased in the PVN only in melancholic depression 26 ; (4) cAMP-response element-binding protein (CREB) that stimulates CRF expression as a transcription factor 27 ; (5) sex hormones, involving estrogen-receptors (ESR) 1 and 2 and androgen-receptor (AR), stimulating and inhibiting CRF gene expression, respectively 28,29 ; (6) the powerful CRF-stimulating proinflammatory cytokines such as interleukin 1-b (IL1b) that is produced by glial cells and PVN neurons, 30 and tumor necrosis factor-a (TNFa), a circulating state marker for depression 31 that is also produced by glial cells 32 ;…”

Increased expression level of corticotropin-releasing hormone in the amygdala and in the hypothalamus in rats exposed to chronic unpredictable mild stress

“…It would be interesting to explore the markers of synapses between CRH neurons in PVN and CeA. CRHR1 has been observed in CRH-positive neurons and its expression is shown to increase after acute stress in rats [38,39] . In our previous postmortem study, we also found an increase of CRHR1 mRNA expression in PVN of depressed patients [40] .…”