Regulation of corticotropin-releasing factor (CRF) type-1 receptor gene expression by CRF in the hypothalamus.
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.
Department of Bioregulation, Institute of Gerontology, Nippon Medical School, Kawasaki 211-8533, Japan.
Shun-ichiro
S
Konishi
Yoko
Y
Kasagi
Harumi
H
Katsumata
Shiro
S
Minami
Toshihiro
T
Imaki
D000818:Animals; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D008845:Microinjections; D009474:Neurons / Q000166:cytology / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism*; D000099052:CRF Receptor, Type 1
D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone