PMID- 11025407
OWN - NLM
STAT- MEDLINE
DCOM- 20001121
LR  - 20171101
IS  - 0028-3835 (Print)
IS  - 0028-3835 (Linking)
VI  - 72
IP  - 3
DP  - 2000 Sep
TI  - Progesterone prevents estradiol-induced dendritic spine formation in cultured 
      hippocampal neurons.
PG  - 133-43
AB  - Estradiol has been shown to cause an increase in dendritic spine density in 
      cultured hippocampal neurons, an effect mediated by downregulation of 
      brain-derived neurotrophic factor (BDNF) and glutamic acid decarboxylase (GAD), 
      and the subsequent phosphorylation of cAMP response element binding protein 
      (CREB) in response to enhanced activity levels. Interestingly, progesterone was 
      shown to counteract the effects of estradiol on dendritic spine density in vivo 
      and in vitro. The present study examined how progesterone may act to block the 
      effects of estradiol in the molecular cascade of cellular events leading to 
      formation of dendritic spines. Progesterone did not affect the estradiol-induced 
      downregulation of BDNF or GAD, but it did block the effect of estradiol on CREB 
      phosphorylation. The latter effects of progesterone on the pCREB response and 
      spine formation were reversed by indomethacin, which prevents the conversion of 
      progesterone to the neurosteroid tetrahydroprogesterone (THP). We therefore 
      examined if the progesterone effects were caused by its active metabolite THP. 
      Progesterone treatment caused a 60-fold increase in THP in the culture medium. 
      THP itself enhanced spontaneous GABAergic activity in patch-clamped cultured 
      neurons. Finally, THP blocked the estradiol-induced increase in spine density. 
      These results suggest that progesterone, through conversion to THP, blocks the 
      effects of estradiol on dendritic spines not via a direct nuclear receptor 
      interaction but by counteracting the enhanced excitability produced by estradiol 
      in the cultured network.
CI  - Copyright 2000 S. Karger AG, Basel.
FAU - Murphy, D D
AU  - Murphy DD
AD  - NINDS, NIH, Bethesda, MD, USA.
FAU - Segal, M
AU  - Segal M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - Switzerland
TA  - Neuroendocrinology
JT  - Neuroendocrinology
JID - 0035665
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 320T6RNW1F (Mifepristone)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - 4TI98Z838E (Estradiol)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - BXO86P3XXW (Pregnanolone)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
RN  - XXE1CET956 (Indomethacin)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cell Size/drug effects/physiology
MH  - Cells, Cultured/cytology/drug effects/metabolism
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Dendrites/*drug effects/*metabolism/ultrastructure
MH  - Drug Interactions/physiology
MH  - Estradiol/*metabolism/pharmacology
MH  - Fetus
MH  - Glutamate Decarboxylase/metabolism
MH  - Hippocampus/*drug effects/*metabolism/ultrastructure
MH  - Indomethacin/pharmacology
MH  - Microscopy, Electron
MH  - Mifepristone/pharmacology
MH  - Neuronal Plasticity/*drug effects/physiology
MH  - Patch-Clamp Techniques
MH  - Pregnanolone/analogs & derivatives/metabolism/pharmacology
MH  - Progesterone/analogs & derivatives/*metabolism/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects/physiology
MH  - gamma-Aminobutyric Acid/metabolism
EDAT- 2000/10/12 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/10/12 11:00
PHST- 2000/10/12 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/10/12 11:00 [entrez]
AID - 54580 [pii]
AID - 10.1159/000054580 [doi]
PST - ppublish
SO  - Neuroendocrinology. 2000 Sep;72(3):133-43. doi: 10.1159/000054580.