Expression of corticotropin-releasing hormone type 1 receptor in paraventricular nucleus after acute stress.
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.
Imaki
T
T
Department of Bioregulation, Institute of Gerontology, Nippon Medical School, Kawasaki, Kanagawa, Japan. timaki@mns.ac.jp
Katsumata
H
H
Miyata
M
M
Naruse
M
M
Imaki
J
J
Minami
S
S
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000235:genetics; D015870:Gene Expression; D017403:In Situ Hybridization; D008297:Male; D010121:Oxytocin / Q000096:biosynthesis; D010286:Paraventricular Hypothalamic Nucleus / Q000737:chemistry / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D013312:Stress, Physiological / Q000378:metabolism*; D014667:Vasopressins / Q000096:biosynthesis
C101628:CP 154526; D016760:Proto-Oncogene Proteins c-fos; D011743:Pyrimidines; D011758:Pyrroles; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D014667:Vasopressins; D010121:Oxytocin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone