PMID- 16917842
OWN - NLM
STAT- MEDLINE
DCOM- 20061018
LR  - 20081121
IS  - 0021-9967 (Print)
IS  - 0021-9967 (Linking)
VI  - 498
IP  - 5
DP  - 2006 Oct 10
TI  - Diminished hypothalamic bdnf expression and impaired VMH function are associated 
      with reduced SF-1 gene dosage.
PG  - 637-48
AB  - In the central nervous system, steroidogenic factor 1 (SF-1) is required for 
      terminal differentiation of neurons within the ventromedial hypothalamus (VMH). 
      Given the importance of this brain region in regulating physiological homeostasis 
      including energy balance, we asked how sf-1 gene dosage affects VMH function. 
      Despite an apparent normal VMH cytoarchitecture, sf-1 heterozygous (+/-) mice 
      exhibited diet-induced obesity when they were group housed with hyperphagia and 
      impaired sympathetic activity. On the basis of previous findings suggesting 
      brain-derived neurotrophic factor (bdnf) as an SF-1 target gene, we assessed the 
      colocalization of SF-1 and BDNF expressing neurons, as well as expression of the 
      four exon-specific bdnf promoter transcripts in the VMH. Indeed, a subset of 
      neurons located primarily in the ventrolateral VMH coexpress SF-1 and BDNF, and 
      in contrast to other brain regions, bdnf I, II, and IV but not III are found. 
      Consistent with these findings, cellular assays showed that SF-1 is able to 
      activate exon I and IV promoters. More important, levels of bdnf I and IV in the 
      VMH were reduced in heterozygous mice similar to levels observed in fasted 
      wild-type mice. Collectively, we propose that a reduction in the sf-1 gene dosage 
      directly affects BDNF levels in the VMH and disrupts normal hypothalamic 
      function.
FAU - Tran, Phu V
AU  - Tran PV
AD  - Department of Physiology, University of California, San Francisco, San Francisco, 
      California 94143, USA.
FAU - Akana, Susan F
AU  - Akana SF
FAU - Malkovska, Irena
AU  - Malkovska I
FAU - Dallman, Mary F
AU  - Dallman MF
FAU - Parada, Luis F
AU  - Parada LF
FAU - Ingraham, Holly A
AU  - Ingraham HA
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Comp Neurol
JT  - The Journal of comparative neurology
JID - 0406041
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Leptin)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Steroidogenic Factor 1)
RN  - 0 (Transcription Factors)
RN  - 0 
      (acetyl-norleucyl(4)-(aspartyl(5)-histidyl(6)-phenylalanyl(7)-arginyl(8)-tryptophyl(9)-lysyl(10))cyclo-alpha-MSH(4-10)amide)
RN  - 0 (steroidogenic factor 1, mouse)
RN  - 581-05-5 (alpha-MSH)
SB  - IM
MH  - Animals
MH  - Body Weight/genetics
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Cold Temperature/adverse effects
MH  - Food Deprivation/physiology
MH  - Gene Expression/*genetics
MH  - Homeodomain Proteins/*physiology
MH  - Immunohistochemistry/methods
MH  - Leptin/blood
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neurons/metabolism
MH  - Oxygen Consumption/genetics
MH  - Promoter Regions, Genetic/physiology
MH  - RNA, Messenger/metabolism
MH  - Receptors, Cytoplasmic and Nuclear/deficiency/*physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
MH  - Steroidogenic Factor 1
MH  - Stress, Physiological/etiology/genetics
MH  - Transcription Factors/deficiency/*physiology
MH  - Ventromedial Hypothalamic Nucleus/cytology/*physiology
MH  - alpha-MSH/analogs & derivatives/pharmacology
EDAT- 2006/08/19 09:00
MHDA- 2006/10/19 09:00
CRDT- 2006/08/19 09:00
PHST- 2006/08/19 09:00 [pubmed]
PHST- 2006/10/19 09:00 [medline]
PHST- 2006/08/19 09:00 [entrez]
AID - 10.1002/cne.21070 [doi]
PST - ppublish
SO  - J Comp Neurol. 2006 Oct 10;498(5):637-48. doi: 10.1002/cne.21070.