title: Prolactin-releasing peptide as a novel stress mediator in the central nervous system.
abstract: 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.
authors.affiliation: Department of Regulation Biology, Faculty of Science, Saitama University, 255 Shimo-ohkubo, Urawa 338-0825, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Maruyama
authors.forename: H
authors.initials: H
authors.lastname: Matsumoto
authors.forename: K
authors.initials: K
authors.lastname: Fujiwara
authors.forename: J
authors.initials: J
authors.lastname: Noguchi
authors.forename: C
authors.initials: C
authors.lastname: Kitada
authors.forename: M
authors.initials: M
authors.lastname: Fujino
authors.forename: K
authors.initials: K
authors.lastname: Inoue
mesh_terms: 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
chemical_list: 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