title: Prolactin receptor knockdown in the rat paraventricular nucleus by a morpholino-antisense oligonucleotide causes hypocalcemia and stress gastric erosion.
abstract: Under acute stress conditions in the rat, there is rapid and transient increase in circulating prolactin (PRL). This leads to an elevated expression of the long form of PRLR (PRLR-L) first in the hypothalamus and the choroid plexus. This increase in PRL is involved in the inhibition of stress-induced hypocalcemia and gastric erosion. In this study we used rat PRL and a PRLR morpholino-antisense oligonucleotide to elucidate the mechanism by which hypothalamic PRLR mediates the inhibition of restraint stress in water (RSW)-induced hypocalcemia and gastric erosion. We found that this effect is largely mediated by PRLRs in the paraventricular nucleus (PVN), medial preoptic nucleus, and ventromedial hypothalamus. We also show that when measured after 7 h of RSW, microinjection of the PRLR antisense oligonucleotide into these areas down-regulates RSW-enhanced expression of PRLR-L protein in the PVN and increases the plasma PRL level, but does not affect plasma levels of another hormone, GH. Furthermore, our experiments demonstrated that under nonstress conditions, knockdown of the PRLR in the PVN significantly lowers circulating Ca2+ levels, but does not affect gastric erosion. These results suggest that PRL acting on the PRLR-L in the PVN is one of the critical pathways for regulating circulating Ca2+ levels under both acute stress and nonstress conditions.
authors.affiliation: Department of Biochemistry and Proteomics, Institute of Genomics and Regenerative Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan. t-fuji@doc.medic.mie-u.ac.jp
authors.forename: Takahiko
authors.initials: T
authors.lastname: Fujikawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Tamura
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kawase
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Mori
authors.forename: Randall R
authors.initials: RR
authors.lastname: Sakai
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Sakuma
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yamaguch
authors.forename: Masato
authors.initials: M
authors.lastname: Ogata
authors.forename: Hideaki
authors.initials: H
authors.lastname: Soya
authors.forename: Kunio
authors.initials: K
authors.lastname: Nakashima
mesh_terms: D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D005753:Gastric Mucosa / Q000473:pathology*; D017353:Gene Deletion; D006996:Hypocalcemia / Q000235:genetics*; D007276:Injections, Intraventricular; D007425:Intracellular Membranes / Q000502:physiology; D008297:Male; D008861:Microsomes / Q000502:physiology; D009025:Morpholines / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology*; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D011981:Receptors, Prolactin / Q000172:deficiency* / Q000235:genetics*; D012149:Restraint, Physical; D013272:Stomach Diseases / Q000235:genetics*; D013315:Stress, Psychological
chemical_list: D009025:Morpholines; D016376:Oligonucleotides, Antisense; D011981:Receptors, Prolactin; D002118:Calcium