title: Changes in neuroactive steroid concentrations after preterm delivery in the Guinea pig.
abstract: BACKGROUND
  Preterm birth is a major cause of neurodevelopmental disorders. Allopregnanolone, a key metabolite of progesterone, has neuroprotective and developmental effects in the brain. The objectives of this study were to measure the neuroactive steroid concentrations following preterm delivery in a neonatal guinea pig model and assess the potential for postnatal progesterone replacement therapy to affect neuroactive steroid brain and plasma concentrations in preterm neonates.
  
  
  METHODS
  Preterm (62-63 days) and term (69 days) guinea pig pups were delivered by cesarean section and tissue was collected at 24 hours. Plasma progesterone, cortisol, allopregnanolone, and brain allopregnanolone concentrations were measured by immunoassay. Brain 5α-reductase (5αR) expression was determined by Western blot. Neurodevelopmental maturity of preterm neonates was assessed by immunohistochemistry staining for myelination, glial cells, and neurons.
  
  
  RESULTS
  Brain allopregnanolone concentrations were significantly reduced after birth in both preterm and term neonates. Postnatal progesterone treatment in preterm neonates increased brain and plasma allopregnanolone concentrations. Preterm neonates had reduced myelination, low birth weight, and high mortality compared to term neonates. Brain 5αR expression was also significantly reduced in neonates compared to fetal expression.
  
  
  CONCLUSIONS
  Delivery results in a loss of neuroactive steroid concentrations resulting in a premature reduction in brain allopregnanolone in preterm neonates. Postnatal progesterone therapy reestablished neuroactive steroid levels in preterm brains, a finding that has implications for postnatal growth following preterm birth that occurs at a time of neurodevelopmental immaturity.
authors.affiliation: 1Mothers and Babies Research Centre, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
authors.forename: Meredith A
authors.initials: MA
authors.lastname: Kelleher
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Hirst
authors.forename: Hannah K
authors.initials: HK
authors.lastname: Palliser
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001724:Birth Weight; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005865:Gestational Age; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006168:Guinea Pigs; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011247:Pregnancy; D011280:Pregnanolone / Q000097:blood; D047928:Premature Birth / Q000097:blood* / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D011374:Progesterone / Q000097:blood / Q000494:pharmacology; D013256:Steroids / Q000097:blood*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D004676:Myelin Basic Protein; D013256:Steroids; D011374:Progesterone; D011280:Pregnanolone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D006854:Hydrocortisone
keywords: allopregnanolone; fetus; neonate; preterm birth; progesterone