Estradiol induces the calcium-dependent translocation of endothelial nitric oxide synthase.

doi:10.1073/PNAS.96.6.2788

Paper

Estradiol induces the calcium-dependent translocation of endothelial nitric oxide synthase.

Published Mar 16, 1999 · R. Goetz, H. Thatte, P. Prabhakar

Proceedings of the National Academy of Sciences of the United States of America

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245

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5

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Abstract

Although estrogen is known to stimulate nitric oxide synthesis in vascular endothelium, the molecular mechanisms responsible for this effect remain to be elucidated. Using quantitative immunofluorescence imaging approaches, we have investigated the effect of estradiol on the subcellular targeting of endothelial nitric oxide synthase (eNOS) in bovine aortic endothelial cells. In unstimulated endothelial cells, eNOS is predominantly localized at the cell membrane. Within 5 min after the addition of estradiol, most of the eNOS translocates from the membrane to intracellular sites close to the nucleus. On more prolonged exposure to estradiol, most of the eNOS returns to the membrane. This effect of estradiol is evident at a concentration of 1 pM, and a maximal estradiol effect is seen at a concentration of 1 nM. Neither progesterone nor testosterone has any effect on eNOS distribution. After estradiol addition, a transient rise in intracellular Ca2+ concentration precedes eNOS translocation. Both the Ca2+-mobilizing and eNOS-translocating effects of estradiol are completely blocked by the estrogen receptor antagonist ICI 182,780, and the intracellular Ca2+ chelator 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) prevents estradiol-induced eNOS translocation. Use of the nitric oxide-specific dye diaminofluorescein shows that estradiol treatment increases nitric oxide generation by endothelial cells; this response is blocked by ICI 182,780 and by the eNOS inhibitor Nomega-nitro-L-arginine. These results show that estradiol induces subcellular translocation of eNOS by a rapid, Ca2+-dependent, receptor-mediated mechanism, and they suggest a nongenomic role for estrogen in the modulation of NO-dependent vascular tone.

In Vitro Study

Highly Cited

Study Snapshot

Estradiol stimulates nitric oxide synthesis in vascular endothelium through a rapid, calcium-dependent, receptor-mediated mechanism, suggesting a nongenomic role for estrogen in NO-dependent vascular tone.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Paper

Estradiol induces the calcium-dependent translocation of endothelial nitric oxide synthase.

References

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Citations

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Sex influences endothelial cell physiology at a genetic level, not just influenced by sex hormones.

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Selective estrogen-receptor modulators, downregulators, phytoestrogens, and non-genomic estrogen-like signaling molecules offer potential treatments for various estrogen-related conditions without causing harmful side effects.

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Endogenous estrogen has cardioprotective and anti-inflammatory effects, but hormone replacement therapies may cause harm, and the optimal time for hormone therapy is pre-menopause and immediately post-menopause.

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Aphidicolin reduces endothelial cell death by increasing nuclear eNOS localization and nitric oxide production, potentially playing a role in maintaining endothelial integrity.

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Gender differences in endothelial function and coronary vasomotion abnormalities have major clinical implications, and understanding these differences can improve healthcare and patient outcomes in cardiovascular medicine.

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Calreticulin is a multifunctional protein with potential therapeutic applications in osteoporosis and anti-thrombotic development.

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Testosterone's non-genomic vascular effects include vasorelaxation and its association with cardiovascular risk factors like metabolic syndrome, type 2 diabetes, obesity, atherosclerosis, dyslipidaemia, and hypertension.