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Equine estrogens impair nitric oxide production and endothelial nitric oxide synthase transcription in human endothelial cells compared with the natural 17{beta}-estradiol.
Abstract: Conjugated equine estrogen therapy is the most common hormone replacement strategy used to treat postmenopausal women. However, the ability of an individual conjugated equine estrogen to modulate NO production and, therefore, to induce cardiovascular protection is largely unknown. The effects of equine and naturally occurring estrogens on NO generation were evaluated in human aortic endothelial cells by measuring in vivo NO production, as well as NO synthase (eNOS) activity and expression. The transcriptional activity on the eNOS gene was determined by the ability of estrogen receptors (alpha and beta) to activate the eNOS promoter and induce transcription. Docking and molecular dynamics simulations were used to study structural features of the interaction between estrogenic compounds and estrogen receptor-alpha. After 24 hours of incubation, we found that estrone upregulated NO production almost as effectively as estradiol by increasing eNOS activity and expression. However, the effect of equine estrogens (equilin, equilenin, and their metabolites) were marked decreased. eNOS promoter activity by equine estrogens was 30% to 50% lower than the naturally occurring estrogens. Computational analysis of estrogen molecules revealed that position 17 and the saturation of estrogenic compounds in ring B are important determinants for estrogen receptor-alpha transcriptional activity. Equine estrogens increase NO production less effectively than naturally occurring estrogens, partially because of their lesser ability to activate the eNOS promoter and induce transcription. Differences in NO production by different estrogens may account for the differences in cardiovascular benefits achieved by the distinct estrogen replacement therapies.
Publication Date: 2010-07-06 PubMed ID: 20606108DOI: 10.1161/HYPERTENSIONAHA.110.151969Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research investigated how equine estrogens (from horse-derived hormone replacement therapy) impact the production of nitric oxide and expression of nitric oxide synthase in human cells, in comparison to naturally occurring 17β-estradiol. The study revealed that equine estrogens, unlike their natural counterparts, can reduce the production of nitric oxide due to their lower ability to activate nitric oxide synthase. This variability in nitric oxide production might explain the varying cardiovascular benefits seen in different estrogen replacement therapies.
Research Methodology And Observations
- The research used human aortic endothelial cells to study the effects of naturally occurring and equine estrogens on nitric oxide (NO) production. This process involved in vivo measurement of NO production, as well as the evaluation of nitric oxide synthase (eNOS) activity and expression.
- The study employed transcriptional activity on the eNOS gene to assess the ability of estrogen receptors (both alpha and beta) in activating the eNOS promoter and in inducing transcription
- Docking and molecular dynamics simulations were used to investigate structural aspects of the interaction between estrogenic compounds and estrogen receptor-alpha.
- After a 24-hour incubation period, researchers observed that estrone, a naturally occurring estrogen, upregulated NO production almost as effectively as estradiol, by increasing eNOS activity and expression.
Findings And Implications
- Equine estrogens (equilin, equilenin, and their metabolites) exhibited a substantial decrease in effect compared to natural estrogens. They only achieved 30% to 50% of the eNOS promoter activity that was possible by naturally occurring estrogens.
- Computational analysis indicated that the saturation and position 17 of estrogenic compounds in ring B play a critical role in determining the transcriptional activity of the estrogen receptor-alpha.
- Equine estrogens were found to be less potent than their natural counterparts in increasing nitric oxide production. This lesser efficiency is partially attributable to their inferior ability to activate the eNOS promoter and induce transcription.
- The different abilities of various estrogens to produce nitric oxide might be the reason behind observed differences in cardiovascular benefits from different estrogen replacement therapies.
Cite This Article
APA
Novensa L, Selent J, Pastor M, Sandberg K, Heras M, Dantas AP.
(2010).
Equine estrogens impair nitric oxide production and endothelial nitric oxide synthase transcription in human endothelial cells compared with the natural 17{beta}-estradiol.
Hypertension, 56(3), 405-411.
https://doi.org/10.1161/HYPERTENSIONAHA.110.151969 Publication
Researcher Affiliations
- Experimental Cardiology Division, Institut d'Investigacions Biomèdiques, August Pi i Sunyer, C/Casanova 143 Lab, IDIBAPS 404, 08036 Barcelona, Spain.
MeSH Terms
- Cells, Cultured
- Endothelial Cells / drug effects
- Endothelial Cells / metabolism
- Estradiol / pharmacology
- Estrogens, Conjugated (USP) / pharmacology
- Humans
- Models, Biological
- Molecular Dynamics Simulation
- Nitric Oxide / biosynthesis
- Nitric Oxide Synthase Type III / genetics
- Nitric Oxide Synthase Type III / metabolism
- Reverse Transcriptase Polymerase Chain Reaction
- Transcription, Genetic / drug effects
Citations
This article has been cited 18 times.- SenthilKumar G, Katunaric B, Bordas-Murphy H, Sarvaideo J, Freed JK. Estrogen and the Vascular Endothelium: The Unanswered Questions. Endocrinology 2023 Apr 17;164(6).
- Gajecki D, Gawryś J, Wiśniewski J, Fortuna P, Szahidewicz-Krupska E, Doroszko A. A Cross-Talk between the Erythrocyte L-Arginine/ADMA/Nitric Oxide Metabolic Pathway and the Endothelial Function in Subjects with Type 2 Diabetes Mellitus. Nutrients 2021 Jul 4;13(7).
- Niu J, Song W, Li R, Yu H, Guan J, Qi J, He Y. The Bdkrb2 gene family provides a novel view of viviparity adaptation in Sebastes schlegelii. BMC Ecol Evol 2021 Mar 17;21(1):44.
- Tashima Y, He H, Cui JZ, Pedroza AJ, Nakamura K, Yokoyama N, Iosef C, Burdon G, Koyano T, Yamaguchi A, Fischbein MP. Androgens Accentuate TGF-β Dependent Erk/Smad Activation During Thoracic Aortic Aneurysm Formation in Marfan Syndrome Male Mice. J Am Heart Assoc 2020 Oct 20;9(20):e015773.
- Filgueira FP, Lobato NS, Nascimento DL, Ceravolo GS, Giachini FRC, Lima VV, Dantas AP, Fortes ZB, Webb RC, Tostes RC, Carvalho MHC. Equilin displays similar endothelium-independent vasodilator potential to 17β-estradiol regardless of lower potential to inhibit calcium entry. Steroids 2019 Jan;141:46-54.
- Jiménez-Altayó F, Siegert AM, Bonorino F, Meirelles T, Barberà L, Dantas AP, Vila E, Egea G. Differences in the Thoracic Aorta by Region and Sex in a Murine Model of Marfan Syndrome. Front Physiol 2017;8:933.
- Bobi J, Solanes N, Fernández-Jiménez R, Galán-Arriola C, Dantas AP, Fernández-Friera L, Gálvez-Montón C, Rigol-Monzó E, Agüero J, Ramírez J, Roqué M, Bayés-Genís A, Sánchez-González J, García-Álvarez A, Sabaté M, Roura S, Ibáñez B, Rigol M. Intracoronary Administration of Allogeneic Adipose Tissue-Derived Mesenchymal Stem Cells Improves Myocardial Perfusion But Not Left Ventricle Function, in a Translational Model of Acute Myocardial Infarction. J Am Heart Assoc 2017 May 3;6(5).
- Berglind IA, Andersen M, Citarella A, Linder M, Sundström A, Kieler H. Hormone therapy and risk of cardiovascular outcomes and mortality in women treated with statins. Menopause 2015 Apr;22(4):369-76.
- Dantas AP, Fortes ZB, de Carvalho MH. Vascular disease in diabetic women: Why do they miss the female protection?. Exp Diabetes Res 2012;2012:570598.
- Jiménez-Altayó F, Onetti Y, Heras M, Dantas AP, Vila E. Western-style diet modulates contractile responses to phenylephrine differently in mesenteric arteries from senescence-accelerated prone (SAMP8) and resistant (SAMR1) mice. Age (Dordr) 2013 Aug;35(4):1219-34.
- Knowlton AA, Lee AR. Estrogen and the cardiovascular system. Pharmacol Ther 2012 Jul;135(1):54-70.
- Caracuel L, Jiménez-Altayó F, Romo M, Márquez-Martín A, Dantas AP, Vila E. Transient mesenteric ischemia leads to remodeling of rat mesenteric resistance arteries. Front Physiol 2011;2:118.
- Srivastava K, Bath PM, Bayraktutan U. Current therapeutic strategies to mitigate the eNOS dysfunction in ischaemic stroke. Cell Mol Neurobiol 2012 Apr;32(3):319-36.
- Novella S, Dantas AP, Segarra G, Novensa L, Heras M, Hermenegildo C, Medina P. Aging enhances contraction to thromboxane A2 in aorta from female senescence-accelerated mice. Age (Dordr) 2013 Feb;35(1):117-28.
- Márquez-Martín A, Jiménez-Altayó F, Dantas AP, Caracuel L, Planas AM, Vila E. Middle cerebral artery alterations in a rat chronic hypoperfusion model. J Appl Physiol (1985) 2012 Feb;112(3):511-8.
- Novensà L, Novella S, Medina P, Segarra G, Castillo N, Heras M, Hermenegildo C, Dantas AP. Aging negatively affects estrogens-mediated effects on nitric oxide bioavailability by shifting ERα/ERβ balance in female mice. PLoS One 2011;6(9):e25335.
- Masood DE, Roach EC, Beauregard KG, Khalil RA. Impact of sex hormone metabolism on the vascular effects of menopausal hormone therapy in cardiovascular disease. Curr Drug Metab 2010 Oct;11(8):693-714.
- Mauvais-Jarvis F, Lindsey SH. Metabolic benefits afforded by estradiol and testosterone in both sexes: clinical considerations. J Clin Invest 2024 Sep 3;134(17).
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