Estrogen increases coagulation factor V mRNA levels via both estrogen receptor-alpha and -beta in murine bone marrow/bone.

• OBJECTIVES: 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.

Keyword

Animals

Blood Coagulation

drug effects

Bone Marrow

physiology

Estradiol

pharmacology

Estrogen Receptor alpha

Estrogen Receptor beta

Factor V

genetics

Female

Gene Expression

drug effects

Liver

physiology

Mice

Mice

Inbred C57BL

Oligonucleotide Array Sequence Analysis

RNA

Messenger

metabolism

Receptors

Estrogen

metabolism

Publication and Content Type

ref (subject category)

art (subject category)