Roles of estrogen in the formation of intracranial aneurysms in ovariectomized female mice.

ABSTRACT:

Background

Epidemiological studies have indicated that postmenopausal women have a higher incidence of intracranial aneurysms than men in the same age group.

Objective

To investigate whether estrogen or estrogen receptors (ERs) mediate protective effects against the formation of intracranial aneurysms.

Methods

Intracranial aneurysms were induced in mice by combining a single injection of elastase into the cerebrospinal fluid with deoxycorticosterone acetate salt hypertension. The mice were treated with estrogen (17β-estradiol), an ERα agonist (propyl pyrazole triol), and an ERβ agonist (diarylpropionitrile) with and without a nitric oxide synthase inhibitor.

Results

The ovariectomized female mice had a significantly higher incidence of aneurysms than the male mice, which was consistent with findings in previous epidemiological studies. In ovariectomized female mice, an ERβ agonist, but not an ERα agonist or 17β-estradiol, significantly reduced the incidence of aneurysms. The protective effect of the ERβ agonist was absent in the ovariectomized ERβ knockout mice. The protective effect of the ERβ agonist was negated by treatment with a nitric oxide synthase inhibitor.

Conclusion

The effects of sex, menopause, and estrogen treatment observed in this animal study were consistent with previous epidemiological findings. Stimulation of estrogen receptor-β was protective against the formation of intracranial aneurysms in ovariectomized female mice.

SUBMITTER: Tada Y 

PROVIDER: S-EPMC4399640 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature