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.

Nyckelord

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

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)