Regulation of Corticotropin-Releasing Factor(CRF) Type-1 Receptor Gene Expression by CRF in the Hypothalamus.

Abstract

We reported previously that acute stress and intracerebroventricular (i.c.v.) injection of corticotropin-releasing factor (CRF) increased neuronal activation and CRF type-1 receptor (CRFR-1) mRNA expression in the CRF-producing neurons of the parvocellular paraventricular nucleus (PVN) of the hypothalamus. In this study, to determine whether CRF can act directly on hypothalamic CRF neurons, thereby increasing CRFR-1 expression, microinjection of CRF into PVN neurons in vivo and primary cultures of dispersed rat fetal hypothalami in vitro were performed. Microinjection of 0.1 microg of CRF into the PVN significantly increased c-fos and CRFR-1 mRNA expression in the CRF-producing parvocellular PVN, 30 min or 180 min after injection, respectively. This effect was blocked by a CRF antagonist, alpha-helical CRF. CRF, when injected into the lateral ventricle at the same dose, increased neither CRFR-1 nor c-fos mRNA levels in the PVN. Primary culture of hypothalamic neurons revealed that CRFR-1 like immunoreactivity was located in CRF-containing neurons, and that the CRFR-1 mRNA level was significantly increased 4 h after incubation with 10(-8) M CRF. These results demonstrate that CRF directly affects hypothalamic neurons to increase CRFR-1 mRNA expression, providing evidence of a direct role for CRF in the regulation of CRFR-1 expression of hypothalamic neurons.

Role of peripheral corticotropin-releasing factor and urocortin II in intestinal inflammation and motility in terminal ileum

“…These results suggest that the differential up-regulation of CRF R1͞R2 may also depend on their ligand rather than TxA treatment as suggested (16). In this regard, CRF and UcnI have been shown to regulate transcription of CRF-R1 in a positivefeedback loop in both central and peripheral cells (32,33). It is also possible that the message up-regulation for CRF-R2 precedes increase in protein levels.…”

Central Type 2 Corticotropin-Releasing Hormone Receptor Mediates Hypothalamic-Pituitary-Adrenocortical Axis Activation in the Rat

“…However, it could be argued that if CRHR-1 plays a major role in the HPA axis activation, the antagonized effects of α-hCRH on each HPA axis that were variably measured in this study should be more potent than those of ASV-30. Previous studies have shown that α-hCRH completely blocked intracerebrovascular CRH induced HPA axis activation or c-fos induction, whereas it partially blocked HPA axis or c-fos responses to various types of stress [22, 23,44,45,46]. It has been postulated that stress activates a number of neurotransmitter systems, including CRH, that in turn increase PVN neuronal activity [47], providing an explanation for the partial antagonizing effects of α-hCRH on the stress-induced HPA axis or c-fos response [45].…”

Listening to mutant mice: a spotlight on the role of CRF/CRF receptor systems in affective disorders

“…Basal expression of CRF 1 mRNA within the PVN is very low. However, in the rat, but not in the mouse, PVN CRF 1 mRNA could be induced via stress exposure or intra-PVN CRF microinfusion (Imaki et al, , 2001Konishi et al, 2003). In the periphery, low levels of CRF 1 mRNA occur in the testis, ovary, retina and adrenal gland.…”