Estrogen increases coagulation factor V mRNA levels via both estrogen receptor-alpha and -beta in murine bone marrow/bone.
OBJECTIVE
Both oral estrogen-based hormone-replacement therapy and contraceptives increase the risk of venous thromboembolism. Several circulating factors involved in coagulation/fibrinolysis are expressed mainly in the liver whilst some are expressed in extrahepatic tissues, including bone marrow. The aim of this study was to identify estrogen-responsive target genes involved in the pathogenesis of estrogen-induced venous thromboembolism.


METHODS
Ovariectomized mice were treated with 17beta-estradiol and possible effects on the expression of genes related to coagulation/fibrinolysis were investigated using DNA microarray analyses.


RESULTS
None of the selected genes was regulated by 17beta-estradiol in the liver. Interestingly, 17beta-estradiol increased mRNA levels of coagulation factor V in the bone marrow/bone. Furthermore, this stimulatory effect of 17beta-estradiol on coagulation factor V expression can be mediated via both estrogen receptor-alpha and -beta.


CONCLUSIONS
The expression of bone marrow-derived, but not liver-derived, coagulation factor V is increased by estrogen treatment in mice. The pathophysiological importance of this finding for estrogen-induced venous thromboembolism remains to be determined.
Division of Endocrinology, Department of Internal Medicine, Sahlgrenska University Hospital, S-41345 Goteborg, Sweden.
Sofia
S
Movérare
Stanko
S
Skrtic
Marie K
MK
Lindberg
Karin
K
Dahlman-Wright
Claes
C
Ohlsson
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001853:Bone Marrow / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005165:Factor V / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D008099:Liver / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D004958:Estradiol; D005165:Factor V