title: Effects of prolactin on hypothalamic supraoptic neurones: evidence for modulation of STAT5 expression and electrical activity.
abstract: OBJECTIVE
  The study investigated the role of prolactin (PRL) in modulating STAT5 and electrical activity of magnocellular neurones in the supraoptic (SO) nucleus of male rats.
  
  
  METHODS
  Evidence of expression of STAT5 in the SO nucleus was investigated by immunocytochemical methods. Effect of blocking prolactin receptors on STAT 5 expression was investigated by Western blotting following transfection of SO neurones with a dominant negative mutant form of the PRL receptor. Prolactin-induced changes in electrical activity were investigated by extracellular recording in hypothalamic slices.
  
  
  RESULTS
  A high proportion of SO neurones in male rats expressed immunoreactive STAT5. Levels of activated STAT5 within the SO nucleus of PRL-treated rats was reduced following transfection with a dominant negative mutant form of the PRL receptor, as compared to rats transfected with wild type PRL receptor. Electrophysiological recordings from the SO nucleus in horizontal brain slices showed that approximately 25% of neurones were responsive to PRL, with both inhibitory and excitatory effects being observed. Cells displaying PRL responses included pharmacologically-identified oxytocinergic neurones.
  
  
  CONCLUSIONS
  Collectively, the results suggest that central PRL targets neurones of the SO nucleus, influencing both activation of the JAK-STAT signalling pathway and neuronal excitability. Whilst the functional significance of this interaction remains to be established, it might be important in co-ordinating oxytocin secretion with physiological events associated with changes in plasma PRL, or in mediating a feedback loop in the oxytocinergic regulation of lactotrophs.
authors.affiliation: Department of Anatomy, University of Bristol, Pre-clinical Veterinary School, Southwell St, Bristol, BS2 8EJ, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Townsend
authors.forename: Belinda J
authors.initials: BJ
authors.lastname: Cave
authors.forename: Michael R
authors.initials: MR
authors.lastname: Norman
authors.forename: Andrea
authors.initials: A
authors.lastname: Flynn
authors.forename: James B
authors.initials: JB
authors.lastname: Uney
authors.forename: Domingo J
authors.initials: DJ
authors.lastname: Tortonese
authors.forename: Jon B
authors.initials: JB
authors.lastname: Wakerley
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004594:Electrophysiology; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008894:Milk Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D011388:Prolactin / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011981:Receptors, Prolactin / Q000378:metabolism; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D013495:Supraoptic Nucleus / Q000166:cytology / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D008894:Milk Proteins; D011981:Receptors, Prolactin; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D011388:Prolactin