PMID- 19805359
OWN - NLM
STAT- MEDLINE
DCOM- 20091228
LR  - 20211020
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 106
IP  - 39
DP  - 2009 Sep 29
TI  - Central role of TRAF-interacting protein in a new model of brain sexual 
      differentiation.
PG  - 16692-7
LID - 10.1073/pnas.0906293106 [doi]
AB  - Sexually dimorphic brain nuclei underlie gender-specific neural functions and 
      susceptibility to disease, but the developmental basis of dimorphisms is poorly 
      understood. In these studies, we focused on the anteroventral periventricular 
      nucleus (AVPV), a nucleus that is larger in females and critical for the 
      female-typical cyclic surge pattern of luteinizing hormone (LH) release. Sex 
      differences in the size and function of the AVPV result from apoptosis that 
      occurs preferentially in the developing male. To identify upstream pathways 
      responsible for sexual differentiation of the AVPV, we used targeted apoptosis 
      microarrays and in vivo and in vitro follow-up studies. We found that the tumor 
      necrosis factor alpha (TNFalpha)-TNF receptor 2 (TNFR2)-NFkappaB cell survival 
      pathway is active in postnatal day 2 (PND2) female AVPV and repressed in male 
      counterparts. Genes encoding key members of this pathway were expressed 
      exclusively in GABAergic neurons. One gene in particular, TNF receptor-associated 
      factor 2 (TRAF2)-inhibiting protein (trip), was higher in males and it inhibited 
      both TNFalpha-dependent NFkappaB activation and bcl-2 gene expression. The male 
      AVPV also had higher levels of bax and bad mRNA, but neither of these genes was 
      regulated by either TNFalpha or TRIP. Finally, the trip gene was not expressed in 
      the sexually dimorphic nucleus of the preoptic area (SDN-POA), a nucleus in which 
      apoptosis is higher in females than males. These findings form the basis of a new 
      model of sexual differentiation of the AVPV that may also apply to the 
      development of other sexually dimorphic nuclei.
FAU - Krishnan, Sudha
AU  - Krishnan S
AD  - Department of Biology, University of Massachusetts-Amherst, 611 North Pleasant 
      Street, Amherst, MA 01003, USA.
FAU - Intlekofer, Karlie A
AU  - Intlekofer KA
FAU - Aggison, Leah K
AU  - Aggison LK
FAU - Petersen, Sandra L
AU  - Petersen SL
LA  - eng
GR  - R01 HD027305/HD/NICHD NIH HHS/United States
GR  - R21 ES013885/ES/NIEHS NIH HHS/United States
GR  - HD 027305/HD/NICHD NIH HHS/United States
GR  - ES 013885/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20090917
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (NF-kappa B)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Tumor Necrosis Factor Receptor-Associated Peptides and Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
SB  - IM
MH  - Animals
MH  - Anterior Hypothalamic Nucleus/metabolism
MH  - Brain/*physiology
MH  - Female
MH  - Genes, bcl-2
MH  - Male
MH  - Models, Biological
MH  - NF-kappa B/genetics/metabolism
MH  - Neurons/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Sex Differentiation
MH  - TNF Receptor-Associated Factor 2/genetics/metabolism
MH  - Tumor Necrosis Factor Receptor-Associated Peptides and 
      Proteins/genetics/*metabolism
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism
MH  - gamma-Aminobutyric Acid/metabolism
PMC - PMC2757835
COIS- The authors declare no conflict of interest.
EDAT- 2009/10/07 06:00
MHDA- 2009/12/29 06:00
PMCR- 2010/03/29
CRDT- 2009/10/07 06:00
PHST- 2009/10/07 06:00 [entrez]
PHST- 2009/10/07 06:00 [pubmed]
PHST- 2009/12/29 06:00 [medline]
PHST- 2010/03/29 00:00 [pmc-release]
AID - 0906293106 [pii]
AID - 9694 [pii]
AID - 10.1073/pnas.0906293106 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2009 Sep 29;106(39):16692-7. doi: 
      10.1073/pnas.0906293106. Epub 2009 Sep 17.