title: Hormonal modulation of endothelial NO production.
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.
authors.affiliation: Pharmacology, University of California, Irvine, School of Medicine, Irvine, CA 92697-4625, USA. spduckle@uci.edu
authors.forename: Sue P
authors.initials: SP
authors.lastname: Duckles
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Miller
mesh_terms: D000728:Androgens / Q000502:physiology; D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology*; D004967:Estrogens / Q000502:physiology; D005260:Female; D005938:Glucocorticoids / Q000502:physiology; D013006:Growth Hormone / Q000502:physiology; D006728:Hormones / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III; D011374:Progesterone / Q000502:physiology; D017526:Receptor, IGF Type 1 / Q000502:physiology; D011972:Receptor, Insulin / Q000502:physiology; D011960:Receptors, Estrogen / Q000502:physiology; D011965:Receptors, Glucocorticoid / Q000502:physiology; D011980:Receptors, Progesterone / Q000502:physiology; D011986:Receptors, Somatotropin / Q000502:physiology
chemical_list: D000728:Androgens; D004967:Estrogens; D005938:Glucocorticoids; D006728:Hormones; D007328:Insulin; D011960:Receptors, Estrogen; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D011986:Receptors, Somatotropin; D009569:Nitric Oxide; D011374:Progesterone; D013006:Growth Hormone; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin