Distribution of mRNAs encoding CRF receptors in brain and pituitary of rat and mouse

Abstract

Two G protein-coupled receptors have been identified that bind corticotropin-releasing factor (CRF) and urocortin (UCN) with high affinity. Hybridization histochemical methods were used to shed light on controversies concerning their localization in rat brain, and to provide normative distributional data in mouse, the standard model for genetic manipulation in mammals. The distribution of CRF-R1 mRNA in mouse was found to be fundamentally similar to that in rat, with expression predominating in the cerebral cortex, sensory relay nuclei, and in the cerebellum and its major afferents. Pronounced species differences in distribution were few, although more subtle variations in the relative strength of R1 expression were seen in several forebrain regions. CRF-R2 mRNA displayed comparable expression in rat and mouse brain, distinct from, and more restricted than that of CRF-R1. Major neuronal sites of CRF-R2 expression included aspects of the olfactory bulb, lateral septal nucleus, bed nucleus of the stria terminalis, ventromedial hypothalamic nucleus, medial and posterior cortical nuclei of the amygdala, ventral hippocampus, mesencephalic raphe nuclei, and novel localizations in the nucleus of the solitary tract and area postrema. Several sites of expression in the limbic forebrain were found to overlap partially with ones of androgen receptor expression. In pituitary, rat and mouse displayed CRF-R1 mRNA signal continuously over the intermediate lobe and over a subset of cells in the anterior lobe, whereas CRF-R2 transcripts were expressed mainly in the posterior lobe. The distinctive expression pattern of CRF-R2 mRNA identifies additional putative central sites of action for CRF and/or UCN. Constitutive expression of CRF-R2 mRNA in the nucleus of the solitary tract, and stress-inducible expression of CRF-R1 transcripts in the paraventricular nucleus may provide a basis for understanding documented effects of CRF-related peptides at a loci shown previously to lack a capacity for CRF-R expression or CRF binding. Other such "mismatches" remain to be reconciled.

Delayed Satiety-Like Actions and Altered Feeding Microstructure by a Selective Type 2 Corticotropin-Releasing Factor Agonist in Rats: Intra-Hypothalamic Urocortin 3 Administration Reduces Food Intake by Prolonging the Post-Meal Interval

“…The observed hypothalamic site of anorectic action for Ucn 3 is supported by neuroanatomical studies, which have observed high levels of CRF 2 receptor synthesis and binding in the rat hypothalamus (Van Pett et al, 2000;Heinrichs et al, 2001). The dorsomedial VMN is rich with CRF 2 receptors (Van Pett et al, 2000) and Ucn 3 terminals (Li et al, 2003), and medial parvocellular (Chalmers et al, 1995) or magnocellular PVN neurons (Van Pett et al, 2000) also reportedly express moderate CRF 2 mRNA levels.…”

“…The dorsomedial VMN is rich with CRF 2 receptors (Van Pett et al, 2000) and Ucn 3 terminals (Li et al, 2003), and medial parvocellular (Chalmers et al, 1995) or magnocellular PVN neurons (Van Pett et al, 2000) also reportedly express moderate CRF 2 mRNA levels. Single-unit recording studies of hypothalamic slices found that stresscopin-related peptide, structurally related to Ucn 2, alters firing rates of neurons in the VMN and PVN, supporting their functional sensitivity to CRF 2 stimulation (Davidowa and Plagemann, 2004).…”

“…In rodents, Ucn 3's putative receptor, CRF 2(a) , is localized in regions that control feeding, including the ventromedial and paraventricular hypothalamic nuclei (VMN, PVN), nucleus tractus solitarius (NTS), medial and posterior cortical amygdala (MeA, CoA), and lateral septum (LS) (Van Pett et al, 2000). To evaluate candidate sites of Ucn 3-CRF 2 anorectic signaling, the present studies infused Ucn 3 into the LV (forebrain) and fourth (hindbrain) ventricle and into feeding-regulatory regions in which Ucn 3 mRNA expression or Ucn 3 terminals occur in proximity to CRF 2 expression.…”

Mouse strain differences in the effects of corticotropin releasing hormone (CRH) on sleep and wakefulness

“…Both CRH and CRH-related neuropeptides exert their influence on CRH 1 and CRH 2 (Lovenberg et al, 1995;Van Pett et al, 2000;Dautzenberg and Hauger, 2002). CRH is relatively selective for the CRH 1 receptor with moderate affinity to the CRH 2 receptor (Timpl et al, 1998) whereas Ucn1 has high affinity to both CRH 1 and CRH 2 receptors (Timpl et al, 1998), but relatively greater affinity for CRH 2 receptors Reyes et al, 2001).…”

Endocrine and behavioural responses to acute central CRF challenge are antagonized in the periphery and CNS, respectively, in C57BL/6 mice

“…central amygdala) and brain stem, inter-connected by CRF-stained fibres in medial forebrain bundle; and scattered CRF-stained cells throughout most areas of the cerebral cortex. An extensive in situ hybridization mapping study of mRNAs for CRF receptor type 1 (CRF-R1) and type 2 (CRF-R2) has been conducted in rat and mouse brains and pituitary glands (Van Pett et al, 2000): in both species, CRF-R1 exhibits high expression in the pituitary and a wide distribution throughout the CNS with regions of high expression including prefrontal cortex, amygdala, bed nucleus of stria terminalis (BNST), septum, basal ganglia, brain stem (e.g. periaqueductal gray, pre-and post-cerebellar regions) and cerebellum.…”