RGD Reference Report - Differential effects of estrogens and progestins on the anticoagulant tissue factor pathway inhibitor in the rat. - Rat Genome Database

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Differential effects of estrogens and progestins on the anticoagulant tissue factor pathway inhibitor in the rat.

Authors: Shirk, RA  Zhang, Z  Winneker, RC 
Citation: Shirk RA, etal., J Steroid Biochem Mol Biol. 2005 Mar;94(4):361-8.
RGD ID: 11062060
Pubmed: PMID:15857755   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jsbmb.2004.12.026   (Journal Full-text)

Oral contraceptives (OC) and postmenopausal hormone therapy (HT) modulate plasma levels of proteins that regulate blood coagulation. It remains unclear whether the progestin component contributes to these changes. The present study was designed to determine whether progestins modulate two essential plasma anticoagulants, antithrombin (AT) and tissue factor pathway inhibitor (TFPI), in an animal model. Ovariectomized rats were treated orally with three progestins, norethindrone acetate (NETA), trimegestone (TMG), or drospirenone (DSP), either alone or combined with 17alpha-ethyinylestradiol (EE). Plasma AT levels were unchanged. However, TFPI activity was reduced by EE alone (10-100 microg/kg/day) in a dose-dependent manner; NETA (3 or 10 mg/kg/day) reduced TFPI by approximately 40 or approximately 80%, respectively, while TMG and DSP had no effect. NETA and EE effects were blocked by co-administration of ICI-182,780, an estrogen receptor antagonist, suggesting that both responses were likely estrogen receptor-mediated. Reduced TFPI after NETA or EE treatment was not accompanied by changes in TFPI mRNA levels in tissues that express TFPI, but there was a positive correlation between plasma TFPI and total cholesterol. Sex hormone effects on TFPI in this model and as reported in women may help to shift the coagulation balance to a more prothrombotic state. Progestins such as TMG and DSP that lack estrogenic activity could potentially have an improved clinical profile.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to estradiol  IEP 11062060 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tfpi  (tissue factor pathway inhibitor)


Additional Information