Abstract
Since the discovery of endothelium-derived relaxing factor and the subsequent identification of nitric oxide (NO) as the primary mediator of endothelium-dependent relaxations, research has focused on chemical and physical stimuli that modulate NO levels. Hormones represent a class of soluble, widely circulating chemical factors that impact production of NO both by rapid effects on the activity of endothelial nitric oxide synthase (eNOS) through phosphorylation of the enzyme and longer term modulation through changes in amount of eNOS protein. Hormones that increase NO production including estrogen, progesterone, insulin, and growth hormone do so through both of these common mechanisms. In contrast, some hormones, including glucocorticoids, progesterone, and prolactin, decrease NO bioavailability. Mechanisms involved include binding to repressor response elements on the eNOS gene, competing for co-regulators common to hormones with positive genomic actions, regulating eNOS co-factors, decreasing substrate for eNOS, and increasing production of oxygen-derived free radicals. Feedback regulation by the hormones themselves as well as the ability of NO to regulate hormonal release provides a second level of complexity that can also contribute to changes in NO levels. These effects on eNOS and changes in NO production may contribute to variability in risk factors, presentation of and treatment for cardiovascular disease associated with aging, pregnancy, stress, and metabolic disorders in men and women.
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Abbreviations
- ACTH:
-
adrenocorticotropic (corticotrophin) hormone
- DHEA:
-
dehydroepiandrosterone
- E2:
-
17β-estradiol
- eNOS:
-
endothelial nitric oxide synthase
- FSH:
-
follicle stimulating hormone
- GH:
-
growth hormone
- Glc:
-
glucocorticoids
- LH:
-
luteinizing hormone
- NO:
-
nitric oxide
- T3:
-
L3,5,3′-triiodothryronine
- T:
-
testosterone
- +:
-
increases in activity
- -:
-
decreases in activity
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Acknowledgments
This work was supported by National Institutes of Health Grants HL-50775 (to SPD) and HL-51736 (to VMM), the Kronos Longevity Research Institute, and the Mayo Foundation.
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Duckles, S.P., Miller, V.M. Hormonal modulation of endothelial NO production. Pflugers Arch - Eur J Physiol 459, 841–851 (2010). https://doi.org/10.1007/s00424-010-0797-1
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DOI: https://doi.org/10.1007/s00424-010-0797-1