Progesterone withdrawal up-regulates vascular endothelial growth factor receptor type 2 in the superficial zone stroma of the human and macaque endometrium: potential relevance to menstruation.
Several reports indicate that vascular endothelial growth factor (VEGF) expression is increased in endometrial glands and stroma during the menstrual phase in the human endometrium. Here we report that VEGF receptor type 2 (KDR), normally expressed only in the vascular endothelium, was dramatically up-regulated in the stromal cells of the superficial endometrial zones during the premenstrual phase in both human and macaque endometrium. This increase was detectable by Northern analysis, in situ hybridization, and immunocytochemistry and was cell specific, zone specific, cycle phase specific, and VEGF receptor type specific. That is, it only occurred during the premenstrual/menstrual phase, did not occur in glandular epithelium, endothelium, or stromal cells of the deepest endometrial zones, and was not observed for VEGF receptor type 1. The upregulation of stromal KDR was induced by progesterone (P) withdrawal in both women and macaques, and adding back P 24 h after P withdrawal in macaques blocked stromal, but not vascular, endothelial KDR expression. Promatrix metalloproteinase-1 (MMP-1) was coordinately up-regulated in the same stromal cell population by P withdrawal. Because of reports that VEGF can enhance MMP expression, we hypothesize that VEGF-KDR interactions may influence MMP expression in the superficial zones of the primate endometrium during the premenstrual phase, and that these interactions play a role in the induction of menstruation.
Nayak
N R
NR
Oregon Regional Primate Research Center, Beaverton 97006, USA.
Critchley
H O
HO
Slayden
O D
OD
Menrad
A
A
Chwalisz
K
K
Baird
D T
DT
Brenner
R M
RM
D000328:Adult; D000818:Animals; D000918:Antibody Specificity; D015152:Blotting, Northern; D015687:Cell Hypoxia; D004717:Endometrium / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008253:Macaca mulatta; D008598:Menstruation / Q000378:metabolism*; D011374:Progesterone / Q000009:adverse effects*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D017978:Receptors, Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D040262:Receptors, Vascular Endothelial Growth Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013256:Steroids / Q000097:blood; D017154:Stromal Cells / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D040281:Vascular Endothelial Growth Factor Receptor-1
D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D013256:Steroids; D011374:Progesterone; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1