Prolactin-releasing peptide as a novel stress mediator in the central nervous system.
A1/A2 noradrenergic neurons in the medulla oblongata are well known to mediate stress signals in the central nervous system. Stress activates A1/A2 noradrenergic neurons, and then noradrenaline (NA) stimulates ACTH secretion through hypothalamic CRH. On the other hand, PRL-releasing peptide (PrRP) was recently isolated and was found to be produced by some A1/A2 neurons and the dorsomedial hypothalamic nucleus. We previously demonstrated that PrRP neurons make synapse-like contact with hypothalamic CRH neurons. In fact, we demonstrated that the central administration of PrRP stimulates CRH-mediated ACTH secretion. Furthermore, it has been reported that PrRP neurons in A1/A2 cell groups are colocalized with tyrosine hydroxylase (TH), which is known as the marker enzyme of catecholaminergic neurons. These data strongly suggest that PrRP is related to stress-responsive signal transduction, and PrRP and NA cooperatively modulate the hypothalamo-pituitary-adrenal axis. We therefore examined the effect of water immersion-restraint stress on c-Fos protein accumulation in PrRP- and TH-immunoreactive neurons. The synergistic effects of PrRP and NA on plasma ACTH elevation were also examined. The results clearly showed that c-Fos protein accumulation dramatically increased in the nuclei of A1/A2 and dorsomedial hypothalamic nucleus PrRP neurons. In addition, it was revealed that c-Fos protein was specifically expressed in the PrRP/TH double positive cells in the A1/A2 cell groups. We also demonstrated that the central administration of PrRP and NA in combination at subactive (noneffective) doses clearly induced plasma ACTH elevation. Here we report that PrRP is a novel and important mediator of the hypothalamo-pituitary-adrenal axis for the stress response.
Maruyama
M
M
Department of Regulation Biology, Faculty of Science, Saitama University, 255 Shimo-ohkubo, Urawa 338-0825, Japan.
Matsumoto
H
H
Fujiwara
K
K
Noguchi
J
J
Kitada
C
C
Fujino
M
M
Inoue
K
K
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001921:Brain / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D007028:Hypothalamic Hormones / Q000032:analysis / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D009479:Neuropeptides / Q000032:analysis / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D056690:Prolactin-Releasing Hormone; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013312:Stress, Physiological / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D007028:Hypothalamic Hormones; D009479:Neuropeptides; C534379:Prlh protein, rat; D056690:Prolactin-Releasing Hormone; D016760:Proto-Oncogene Proteins c-fos; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine