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Journal of Neuroscience, Vol 15, 6340-6350, Copyright © 1995 by Society for Neuroscience
Localization of novel corticotropin-releasing factor receptor (CRF2) mRNA expression to specific subcortical nuclei in rat brain: comparison with CRF1 receptor mRNA expression
DT Chalmers, TW Lovenberg and EB De Souza
Neurocrine Biosciences Inc., San Diego, California 92121, USA.
Corticotropin-releasing factor (CRF) is the primary factor involved in
controlling the release of ACTH from the anterior pituitary and also acts
as a neurotransmitter in a variety of brain systems. The actions of CRF are
mediated by G-protein coupled membrane bound receptors and a high affinity
CRF receptor, CRF1, has been previously cloned and functionally
characterized. We have recently isolated a cDNA encoding a second member of
the CRF receptor family, designated CRF2, which displays approximately 70%
homology at the nucleotide level to the CRF1 receptor and exhibits a
distinctive pharmacological profile. The present study utilized in situ
hybridization histochemistry to localize the distribution of CRF2 receptor
mRNA in rat brain and pituitary gland and compared this with the
distribution of CRF1, receptor expression. While CRF1 receptor expression
was very high in neocortical, cerebellar, and sensory relay structures,
CRF2 receptor expression was generally confined to subcortical structures.
The highest levels of CRF2 receptor mRNA in brain were evident within the
lateral septal nucleus, the ventromedial hypothalamic nucleus and the
choroid plexus. Moderate levels of CRF2 receptor expression were evident in
the olfactory bulb, amygdaloid nuclei, the paraventricular and suraoptic
nuclei of the hypothalamus, the inferior colliculus and 5-HT-associated
raphe nuclei of the midbrain. CRF2-expressing cells were also evident in
the bed nucleus of the stria terminalis, the hippocampal formation and
anterior and lateral hypothalmic areas. In addition, CRF2 receptor mRNA was
also found in cerebral arterioles throughout the brain. Within the
pituitary gland, CRF2 receptor mRNA was detectable only at very low levels
in scattered cells while CRF1 receptor mRNA was readily detectable in
anterior and intermediate lobes. This heterogeneous distribution of CRF1
and CRF2 receptor mRNA suggests distinctive functional roles for each
receptor in CRF-related systems. The CRF1 receptor may be regarded as the
primary neuroendocrine pituitary CRF receptor and important in cortical,
cerebellar and sensory roles of CRF. The anatomical distribution of CRF2
receptor mRNA indicates a role for this novel receptor in hypothalamic
neuroendocrine, autonomic and general behavioral actions of central CRF.
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Transcriptional Regulation of Corticotropin-Releasing Hormone-Binding Protein Gene Expression in Astrocyte Cultures
Endocrinology,
September 1, 1999;
140(9):
4095 - 4103.
[Abstract]
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D. Engler, E. Redei, and I. Kola
The Corticotropin-Release Inhibitory Factor Hypothesis: A Review of the Evidence for the Existence of Inhibitory as Well as Stimulatory Hypophysiotropic Regulation of Adrenocorticotropin Secretion and Biosynthesis
Endocr. Rev.,
August 1, 1999;
20(4):
460 - 500.
[Abstract]
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