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Publication : Age-dependent bimodal GDNF regulation during ovarian tumorigenesis in follitropin receptor mutant mice.

First Author  Aravindakshan J Year  2006
Journal  Biochem Biophys Res Commun Volume  351
Issue  2 Pages  507-13
PubMed ID  17069759 Mgi Jnum  J:116547
Mgi Id  MGI:3694497 Doi  10.1016/j.bbrc.2006.10.069
Citation  Aravindakshan J, et al. (2006) Age-dependent bimodal GDNF regulation during ovarian tumorigenesis in follitropin receptor mutant mice. Biochem Biophys Res Commun 351(2):507-13
abstractText  Most ovarian tumors in women occur upon aging. Follitropin receptor knockout (FORKO) mice are sterile and have age-dependent abnormalities including increased ovarian tumor incidence. To explore why atrophic ovaries of FORKO mice become tumorigenic later in life, we compared gene expression profiles by microarray at different ages. Here we show an unexpected ovarian expression of GDNF and its bimodal regulation. GDNF was down-regulated at a young age but up-regulated in aging FORKO mice prior to tumor appearance. Immunohistochemistry localized GDNF in the oocyte as well as somatic granulosa and stromal cells. GDNF protein also showed an age-dependent increase in the ovary, being lower in young mutants and increasing by 6 months. We found evidence for GDNF up-regulation in GC tumors and a potential role for androgen. The peripheral expression pattern and functions of this powerful neurotropic factor suggest mediation of processes involved in pathology of ovarian compartments.
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