Endothelial cell dysfunction following prolonged activation of progesterone receptor.
Progestin-only contraceptives are associated with breakthrough bleeding in up to 50% of users. The causes of blood vessel rupture are not well understood. Here we report that both normal and Norplant-exposed endothelium express progesterone receptor. Experiments performed in vitro on endothelial cells isolated from human endometrium revealed that longterm progesterone exposure leads to suppression of endothelial cell proliferation, inhibition of migration and alteration in the profile of extracellular matrix proteins secreted by human endometrial endothelial cells. In addition, we detected increased levels of matrix metalloproteinase-9 in endothelial cultures treated with progesterone. The effect of progesterone on the cell cycle, along with the increased amounts of matrix-degrading enzymes, could account for breakdown of basement membrane components, vascular fragility and consequent vessel rupture leading to breakthrough endometrial bleeding.
Rodríguez-Manzaneque
J C
JC
Department of Molecular, Cell and Developmental Biology, and Molecular Biology Institute, University of California, Los Angeles 90095, USA.
Graubert
M
M
Iruela-Arispe
M L
ML
D000293:Adolescent; D000328:Adult; D001485:Basement Membrane / Q000187:drug effects; D004717:Endometrium / Q000098:blood supply*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology*; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D045167:Progesterone Congeners / Q000494:pharmacology; D011397:Promegestone / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011980:Receptors, Progesterone / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D014592:Uterine Hemorrhage / Q000139:chemically induced / Q000503:physiopathology
D045167:Progesterone Congeners; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D011374:Progesterone; D016912:Levonorgestrel; D011397:Promegestone; D020780:Matrix Metalloproteinase 9