Document Detail

Changes in neuroactive steroid concentrations after preterm delivery in the Guinea pig.
MedLine Citation:
PMID:  23585339     Owner:  NLM     Status:  MEDLINE    
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.
Meredith A Kelleher; Jonathan J Hirst; Hannah K Palliser
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-04-12
Journal Detail:
Title:  Reproductive sciences (Thousand Oaks, Calif.)     Volume:  20     ISSN:  1933-7205     ISO Abbreviation:  Reprod Sci     Publication Date:  2013 Nov 
Date Detail:
Created Date:  2013-10-11     Completed Date:  2014-03-17     Revised Date:  2014-11-04    
Medline Journal Info:
Nlm Unique ID:  101291249     Medline TA:  Reprod Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1365-75     Citation Subset:  IM    
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MeSH Terms
3-Oxo-5-alpha-Steroid 4-Dehydrogenase / metabolism
Animals, Newborn
Birth Weight
Brain / drug effects,  growth & development,  metabolism*,  pathology
Disease Models, Animal
Gestational Age
Glial Fibrillary Acidic Protein / metabolism
Guinea Pigs
Hydrocortisone / blood
Microtubule-Associated Proteins / metabolism
Myelin Basic Protein / metabolism
Myelin Sheath / metabolism
Neuroglia / metabolism
Neurons / metabolism
Pregnanolone / blood
Premature Birth / blood*,  drug therapy,  pathology,  physiopathology
Progesterone / blood,  pharmacology
Steroids / blood*
Reg. No./Substance:
0/Glial Fibrillary Acidic Protein; 0/Microtubule-Associated Proteins; 0/Myelin Basic Protein; 0/Steroids; 4G7DS2Q64Y/Progesterone; BXO86P3XXW/Pregnanolone; EC 4-Dehydrogenase; WI4X0X7BPJ/Hydrocortisone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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