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Fibroblast
Growth Factor Receptor-1 Is a Critical Component for Endometrial Remodeling:
Localization and Expression of Basic Fibroblast Growth Factor and FGF-R1
in Human Endometrium during the Menstrual Cycle and Decreased FGF-R1 Expression
in Menorrhagia |
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Rajbant K.
Sangha, Xiao Feng Li, Munjiba Shams, and Asif Ahmed |
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Reproductive
Physiopathology Group, Department of Obstetrics and Gynecology, University
of Birmingham, Birmingham Women's Hospital, Edgbaston, Birmingham, United
Kingdom |
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Angiogenic growth factors
play a critical role in the cyclic growth and vascularization of normal
endometrium. Herein, we report the expression and localization of both basic
fibroblast growth factor (FGF-2) and its receptor (FGF-R1; flg) in human
endometrium and demonstrate the markedly decreased FGF-R1 levels in menorrhagia.
In situ hybridization using [35S]-labeled riboprobe demonstrated distinct
autoradiographic signals for FGF-2 mRNA in glandular epithelial and stromal
cells in endometrium throughout the menstrual cycle, with the strongest
hybridization signal in stromal cells of the proliferative endometrium relative
to that of the secretory endometrium. Moreover, RNAse protection assay revealed
that the mRNA encoding FGF-2 and FGF-R1 was significantly higher in proliferative
than in secretory endometrium (p < 0.05, p < 0.01). Immunohistochemistry
using anti-flg antibody showed that the intensity of FGF-R1 staining was
markedly diminished in the stromal cells of secretory endometrium, which
corresponded with the reduced FGF-2 mRNA expression. In contrast, the endometrial
glandular epithelial cells showed intense localization of FGF-R1 protein
throughout the menstrual cycle, which paralleled FGF-2 mRNA expression.
Colocalization of FGF-2 and FGF-R1 in stroma and stimulation of DNA synthesis
and phospholipase C activation by FGF-2 in these cells demonstrates that
FGF-2 acts in an autocrine manner in endometrial stroma. Western immunoblotting
showed that FGF-R1 immunoprotein was markedly reduced or absent in women
with menorrhagia throughout the cycle relative to that of normal cycling
women, suggesting that FGF-R1 is critical for endometrial "maturation''
and regeneration of the normal endometrium following menstruation. |
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