title: Vasotocin and mesotocin stimulate the biosynthesis of neurosteroids in the frog brain.
abstract: The neurohypophysial nonapeptides vasopressin (VP) and oxytocin (OT) modulate a broad range of cognitive and social activities. Notably, in amphibians, vasotocin (VT), the ortholog of mammalian VP, plays a crucial role in the control of sexual behaviors. Because several neurosteroids also regulate reproduction-related behaviors, we investigated the possible effect of VT and the OT ortholog mesotocin (MT) in the control of neurosteroid production. Double immunohistochemical labeling of frog brain sections revealed the presence of VT/MT-positive fibers in close proximity of neurons expressing the steroidogenic enzymes 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase (3beta-HSD) and cytochrome P450 17alpha-hydroxylase/c17, 20-lyase (P450(C17)). High concentrations of VT and MT receptor mRNAs were observed in diencephalic nuclei containing the 3beta-HSD and P450(C17) neuronal populations. Exposure of frog hypothalamic explants to graded concentrations of VT or MT produced a dose-dependent increase in the formation of progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, and dehydroepiandrosterone. The stimulatory effect of VT and MT on neurosteroid biosynthesis was mimicked by VP and OT, as well as by a selective V1b receptor agonist, whereas V2 and OT receptor agonists had no effect. VT-induced neurosteroid production was completely suppressed by selective V1a receptor antagonists and was not affected by V2 and OT receptor antagonists. Concurrently, the effect of MT on neurosteroidogenesis was markedly attenuated by selective OT and V1a receptor antagonists but not by a V2 antagonist. The present study provides the first evidence for a regulatory effect of VT and MT on neurosteroid biosynthesis. These data suggest that neurosteroids may mediate some of the behavioral actions of VT and MT.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 413, Laboratory of Cellular and Molecular Neuroendocrinology, European Institute for Peptide Research, University of Rouen, 76821 Mont-Saint-Aignan, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Do-Rego
authors.forename: Sujata
authors.initials: S
authors.lastname: Acharjee
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Seong
authors.forename: Ludovic
authors.initials: L
authors.lastname: Galas
authors.forename: David
authors.initials: D
authors.lastname: Alexandre
authors.forename: Patrice
authors.initials: P
authors.lastname: Bizet
authors.forename: Arlette
authors.initials: A
authors.lastname: Burlet
authors.forename: Hyuk Bang
authors.initials: HB
authors.lastname: Kwon
authors.forename: Van
authors.initials: V
authors.lastname: Luu-The
authors.forename: Georges
authors.initials: G
authors.lastname: Pelletier
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004563:Electrochemistry / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D010120:Oxytocics / Q000494:pharmacology*; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011893:Rana esculenta; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013256:Steroids / Q000096:biosynthesis*; D014668:Vasotocin / Q000494:pharmacology*
chemical_list: D010120:Oxytocics; D012333:RNA, Messenger; D013256:Steroids; C001713:mesotocin; D010121:Oxytocin; D014668:Vasotocin