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Aguillón Osma, J., Bedoya Blandón, Ángela M., Loango Chamorro, N., & Landázuri, P. (2018). Niveles de estradiol en niños y jóvenes y su relación con género, edad, presión arterial, lípidos plasmáticos y polimorfismo XbaI del receptor de estrógenos. Biosalud, 17(1), 19–30. https://doi.org/10.17151/biosa.2018.17.1.3
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La identificación de factores de riesgo para las enfermedades cardiovasculares (ECV) puede ayudar a prevenir su desarrollo. Las hormonas esteroides a través de sus receptores y las variaciones genéticas influyen sobre el metabolismo de los lípidos y la presión arterial, entre otras funciones. Métodos: Estudio descriptivo realizado en niños y adolescentes entre 8 y 18 años de edad. Objetivo: Determinar los niveles de estradiol y su relación con género, edad, presión arterial, lípidos plasmáticos y polimorfismo XbaI del receptor de estrógenos. Resultados: No se encontró relación estadística entre el polimorfismo XbaI y las concentraciones de estradiol, pero sí entre el polimorfismo y el perfil lipídico, de igual manera entre las concentraciones de esta hormona con triglicéridos y c-VLDL. Conclusión: Este trabajo evidencia la relación entre niveles de estrógenos, edad, presión sanguínea y lípidos plasmáticos, de igual forma demuestra una relación entre polimorfismo XbaI del ESR1 y los niveles de lípidos.
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7. Tomaszewski M, Charchar FJ, Maric C, Kuzniewicz R, Gola M, Grzeszczak W, et al. Association between lipid profile and circulating concentrations of estrogens in young men. Atherosclerosis. 2009;203(1):257-262. doi: 10.1016/j.atherosclerosis.2008.06.002.
8. Chakrabarti S, Morton JS, Davidge ST. Mechanisms of estrogen effects on the endothelium: an overview. Can J Cardiol. 2014;30(7):705-712. doi: 10.1016/j.cjca.2013.08.006.
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11. Kong BWC, Vanhoutte PM, Man RYK, Leung SWS. 17β-estradiol potentiates endothelium-dependent nitric oxide- and hyperpolarization-mediated relaxations in blood vessels of male but not female apolipoprotein-E deficient mice. Vascul Pharmacol. 2015;71:166-173. doi: 10.1016/j.vph.2015.02.009.
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15. Frick KM. Molecular mechanisms underlying the memory-enhancing effects of estradiol. Horm Behav. 2015;74:4-18. doi: 10.1016/j.yhbeh.2015.05.001.
16. Welboren WJ, Sweep FCGJ, Span PN, Stunnenberg HG. Genomic actions of estrogen receptor alpha: what are the targets and how are they regulated? Endocr Relat Cancer. 2009;16(4):1073-1089. doi: 10.1677/ERC-09-0086.
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20. Skouby SO, Endrikat J, Düsterberg B, Schmidt W, Gerlinger C, Wessel J, et al. A 1-year randomized study to evaluate the effects of a dose reduction in oral contraceptives on lipids and carbohydrate metabolism: 20 microg ethinyl estradiol combined with 100 microg levonorgestrel. Contraception. 2005;71(2):111-117. doi: 10.1016/j.contraception.2004.08.017.
21. Golden SH, Kim C, Barrett-Connor E, Nan B, Kong S, Goldberg R. The association of elective hormone therapy with changes in lipids among glucose intolerant postmenopausal women in the diabetes prevention program. Metabolism. 2013;62(9):1313-1322. doi: 10.1016/j.metabol.2013.04.005.
22. Dai W, Ming W, Li Y, Zheng HY, Wei CD, Rui Z, et al. Synergistic Effect of a Physiological Ratio of Estradiol and Testosterone in the Treatment of Early-stage Atherosclerosis. Arch Med Res. 2015;46(8):619- 629. doi: 10.1016/j.arcmed.2015.11.003.
23. Almeida-Pereira G, Coletti R, Mecawi AS, Reis LC, Elias LLK, Antunes-Rodrigues J. Estradiol and angiotensin II crosstalk in hydromineral balance: Role of the ERK1/2 and JNK signaling pathways. Neuroscience. 2016;322:525-538. doi: 10.1016/j.neuroscience.2016.02.067.
24. Rokach A, Pollak A, Rosen L, Friedlander Y, Blumenfeld A, Reznik L, et al. Estrogen receptor alpha gene polymorphisms are associated with the angiographic extent of coronary artery disease. J Clin Endocrinol Metab. 2005;90(12):6556-6560. doi: 10.1210/jc.2005-0236.
25. Rubio M, Moreno C, Cabrerizo L. Guías para el tratamiento de las dislipemias en el adulto: Adult Treatment Panel III (ATP-III). Endocrinol y Nutr. 2004;51(05):254-266. doi: 10.1016/S1575-0922(04)74614-8.
26. Paris F, Servant N, Térouanne B, Balaguer P, Nicolas JC, Sultan C. A new recombinant cell bioassay for ultrasensitive determination of serum estrogenic bioactivity in children. J Clin Endocrinol Metab. 2002;87(2):791-797. doi: 10.1210/jc.87.2.791.
27. Aksglaede L, Juul A, Leffers H, Skakkebæk NE, Andersson AM. The sensitivity of the child to sex steroids: Possible impact of exogenous estrogens. Hum Reprod Update. 2006;12(4):341-349. doi: 10.1093/humupd/dml018.
28. Abd El-Meseeh NA, El-Shaarawy EAA, AlDomairy AF, Sehly RAA. Changes in rat testis morphology and androgen receptor expression around the age of puberty. Ann Anat. 2016;205:37-44. doi: 10.1016/j.aanat.2016.01.003.
29. Larmore KA, O’Connor D, Sherman TI, Funanage VL, Hassink SG, Klein KO. Leptin and estradiol as related to change in pubertal status and body weight. Med Sci Monit. 2002;8(3):CR206-CR210. doi:2292 [pii].
30. Klein KO, Baron J, Colli MJ, Mcdonnell DP, Cutler GB. Estrogen Levels in Childhood Determined by an Ultrasensitive Recombinant Cell Bioassay. 1994;94(6):2475-2480.
31. Hall JE. Endocrinology of the Menopause. Endocrinol Metab Clin North Am. 2015;44(3):485-496. doi: 10.1016/j.ecl.2015.05.010.
32. Buck Louis GM, Gray LE, Marcus M, Ojeda SR, Pescovitz OH, Witchel SF, et al. Environmental Factors and Puberty Timing: Expert Panel Research Needs. Pediatrics. 2008;121(Suppl 3):S192-S207. doi: 10.1542/peds.1813E.
33. Atwood CS, Meethal SV. The spatiotemporal hormonal orchestration of human folliculogenesis, early embryogenesis and blastocyst implantation. Mol Cell Endocrinol. 2016;430:33-48. doi: 10.1016/j.mce.2016.03.039.
34. Landázuri P, Granobles C, Loango N. Gender Differences in Serum Angiotensin-Converting Enzyme Activity and Blood Pressure in Children: an Observational Study. Arq Bras Cardiol. 2008;6(91):352- 357.
35. Gaete X, Codner E. Adelanto de la pubertad en Chile y el mundo. Rev Chil pediatría. 2006;77(5):456- 465. doi: 10.4067/S0370-41062006000500002.
36. Mompeón A, Lázaro-Franco M, Bueno-Betí C, Pérez-Cremades D, Vidal-Gómez X, Monsalve E, et al. Estradiol, acting through ERα, induces endothelial non-classic renin-angiotensin system increasing angiotensin 1-7 production. Mol Cell Endocrinol. 2016;422:1-8. doi: 10.1016/j.mce.2015.11.004.
37. Curtis KS. Estradiol and osmolality: Behavioral responses and central pathways. Physiol Behav. 2015;152(Pt B):422-430. doi: 10.1016/j.physbeh.2015.06.017.
38. Kamper M, Manns CC, Plieschnig JA, Schneider WJ, Ivessa NE, Hermann M. Estrogen enhances secretion of apolipoprotein B-100 containing lipoproteins by BeWo cells. Biochimie. 2015;112:121-128. doi: 10.1016/j.biochi.2015.03.002.
39. Palmeira AC, Leal AA de F, Ramos N de MN, Neto J de AF, Simoes MO da S, Medeiros CCM. Lipoprotein (a) and cardiovascular risk factors in children and adolescents. Rev Paul Pediatr. 2013;31(4):531-537. doi: 10.1590/S0103-05822013000400017.
40. Ohta T, Hattori S, Murakami M, Nishiyama S, Matsuda I. Age- and Sex-related Differences inLipoproteins Containing Apoprotein A-I. Arteriosclerosis Thromb Vasc Biol. 1989;9:90-95. doi: 10.1161/01.ATV.9.1.90.
41. Pelegrini A, Glaner MF, Petroski EL. Association between anthropometric indicators and serum lipid profile in adolescents. Hum Mov. 2012;13(3):242-246. doi: 10.2478/v10038-012-0028-z.
42. Persson L, Henriksson P, Westerlund E, Hovatta O, Angelin B, Rudling M. Endogenous estrogens lower plasma PCSK9 and LDL cholesterol but not Lp(a) or bile acid synthesis in women. Arterioscler Thromb Vasc Biol. 2012;32(3):810-814. doi: 10.1161/ATVBAHA.111.242461.
43. Hussain Y, Ding Q, Connelly PW, Brunt JH, Ban MR, McIntyre AD, et al. G-protein estrogen receptor as a regulator of low-density lipoprotein cholesterol metabolism: Cellular and population genetic studies. Arterioscler Thromb Vasc Biol. 2015;35(1):213-221. doi: 10.1161/ATVBAHA.114.304326.
44. Simoncini T, Mannella P, Fornari L, Caruso A, Willis MY, Garibaldi S, et al. Differential signal transduction of progesterone and medroxyprogesterone acetate in human endothelial cells. Endocrinology. 2004;145(12):5745-5756. doi: 10.1210/en.2004-0510.
45. Urbina EM, McCoy CE, Gao Z, Khoury PR, Shah AS, Dolan LM, et al. Lipoprotein particle number and size predict vascular structure and function better than traditional lipids in adolescents and young adults. J Clin Lipidol. 2017;11(4):1023-31. doi: 10.1016/j.jacl.2017.05.011.
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2. Xu B, Lovre D, Mauvais-Jarvis F. Effect of selective estrogen receptor modulators on metabolic homeostasis. Biochimie. 2016;124:92-97. doi: 10.1016/j.biochi.2015.06.018.
3. Del Principe D, Ruggieri A, Pietraforte D, Villani A, Vitale C, Straface C, et al. The relevance of estrogen/estrogen receptor system on the gender difference in cardiovascular risk. Int J Cardiol. 2015;187:291-298. doi: 10.1016/j.ijcard.2015.03.145.
4. Khalid AB, Krum SA. Estrogen receptors alpha and beta in bone. Bone. 2016;87:130-135. doi: 10.1016/j.bone.2016.03.016.
5. Efstathiadou ZA, Sakka C, Polyzos SA, Goutou M, Stakias N, Bargiota A, et al. Associations of estrogen receptor alpha and Beta gene polymorphisms with lipid levels and insulin resistance in men. Metabolism. 2015;64(5):611-617. doi: 10.1016/j.metabol.2015.01.006.
6. Boroumand M, Ghaedi M, Mohammadtaghvaei N, Pourgholi L, Anvari MS, Davoodi G, et al. Lipid profile and inflammatory markers associated with estrogen receptor alpha PvuII and XbaI gene polymorphisms. Transl Res. 2009;153(6):288-295. doi: 10.1016/j.trsl.2009.02.006.
7. Tomaszewski M, Charchar FJ, Maric C, Kuzniewicz R, Gola M, Grzeszczak W, et al. Association between lipid profile and circulating concentrations of estrogens in young men. Atherosclerosis. 2009;203(1):257-262. doi: 10.1016/j.atherosclerosis.2008.06.002.
8. Chakrabarti S, Morton JS, Davidge ST. Mechanisms of estrogen effects on the endothelium: an overview. Can J Cardiol. 2014;30(7):705-712. doi: 10.1016/j.cjca.2013.08.006.
9. Muka T, Vargas KG, Jaspers L, Wen KX, Dhana K, Vitezova A, et al. Estrogen receptor β actions in the female cardiovascular system: A systematic review of animal and human studies. Maturitas. 2016;86:28-43. doi: 10.1016/j.maturitas.2016.01.009.
10. Tarhouni K, Guihot AL, Vessieres E, Procaccio V, Grimaud L, Abraham P, et al. Estrogens are needed for the improvement in endothelium-mediated dilation induced by a chronic increase in blood flow in rat mesenteric arteries. Vascul Pharmacol. 2016;80:35-42. doi: 10.1016/j.vph.2015.10.004.
11. Kong BWC, Vanhoutte PM, Man RYK, Leung SWS. 17β-estradiol potentiates endothelium-dependent nitric oxide- and hyperpolarization-mediated relaxations in blood vessels of male but not female apolipoprotein-E deficient mice. Vascul Pharmacol. 2015;71:166-173. doi: 10.1016/j.vph.2015.02.009.
12. Oliveras A, Sans-Atxer L, Vázquez S. [Is blood pressure control different in women than in en?]. Hipertens y riesgo Vasc. 2015;32(4):151-158. doi: 10.1016/j.hipert.2015.08.001.
13. Hewitt SC, Winuthayanon W, Korach KS. What’s new in estrogen receptor action in the female reproductive tract. J Mol Endocrinol. 2016;56(2):R55-R71. doi: 10.1530/JME-15-0254.
14. Ervin KSJ, Phan A, Gabor CS, Choleris E. Rapid oestrogenic regulation of social and nonsocial learning. J Neuroendocrinol. 2013;25(11):1116-1132. doi: 10.1111/jne.12079.
15. Frick KM. Molecular mechanisms underlying the memory-enhancing effects of estradiol. Horm Behav. 2015;74:4-18. doi: 10.1016/j.yhbeh.2015.05.001.
16. Welboren WJ, Sweep FCGJ, Span PN, Stunnenberg HG. Genomic actions of estrogen receptor alpha: what are the targets and how are they regulated? Endocr Relat Cancer. 2009;16(4):1073-1089. doi: 10.1677/ERC-09-0086.
17. Silva FS, Sóter MO, Sales MF, Candido AL, Reis FM, Silva IF, et al. Estrogen receptor αlpha gene (ESR1) PvuII and XbaI polymorphisms are associated to metabolic and proinflammatory factors in polycystic ovary syndrome. Gene. 2015;560(1):44-49. doi: 10.1016/j.gene.2015.01.037.
18. Araújo KL, Cunha L, Soncini L, Dalmashio R, Pirola K, Ferreira M, et al. Prevalence of Estrogen Receptor Alpha PvuII (c454- 397T > C) and XbaI (c454A > G) Polymorphisms in a Population of Brazilian Women. Braz Arch Biol Technol. 2011;54(6):1151-1157.
19. Brynhildsen J, Hammar M. Lipids and clotting factors during low dose transdermal estradiol/norethisterone use. Maturitas. 2005;50(4):344-352. doi: 10.1016/j.maturitas.2004.10.001.
20. Skouby SO, Endrikat J, Düsterberg B, Schmidt W, Gerlinger C, Wessel J, et al. A 1-year randomized study to evaluate the effects of a dose reduction in oral contraceptives on lipids and carbohydrate metabolism: 20 microg ethinyl estradiol combined with 100 microg levonorgestrel. Contraception. 2005;71(2):111-117. doi: 10.1016/j.contraception.2004.08.017.
21. Golden SH, Kim C, Barrett-Connor E, Nan B, Kong S, Goldberg R. The association of elective hormone therapy with changes in lipids among glucose intolerant postmenopausal women in the diabetes prevention program. Metabolism. 2013;62(9):1313-1322. doi: 10.1016/j.metabol.2013.04.005.
22. Dai W, Ming W, Li Y, Zheng HY, Wei CD, Rui Z, et al. Synergistic Effect of a Physiological Ratio of Estradiol and Testosterone in the Treatment of Early-stage Atherosclerosis. Arch Med Res. 2015;46(8):619- 629. doi: 10.1016/j.arcmed.2015.11.003.
23. Almeida-Pereira G, Coletti R, Mecawi AS, Reis LC, Elias LLK, Antunes-Rodrigues J. Estradiol and angiotensin II crosstalk in hydromineral balance: Role of the ERK1/2 and JNK signaling pathways. Neuroscience. 2016;322:525-538. doi: 10.1016/j.neuroscience.2016.02.067.
24. Rokach A, Pollak A, Rosen L, Friedlander Y, Blumenfeld A, Reznik L, et al. Estrogen receptor alpha gene polymorphisms are associated with the angiographic extent of coronary artery disease. J Clin Endocrinol Metab. 2005;90(12):6556-6560. doi: 10.1210/jc.2005-0236.
25. Rubio M, Moreno C, Cabrerizo L. Guías para el tratamiento de las dislipemias en el adulto: Adult Treatment Panel III (ATP-III). Endocrinol y Nutr. 2004;51(05):254-266. doi: 10.1016/S1575-0922(04)74614-8.
26. Paris F, Servant N, Térouanne B, Balaguer P, Nicolas JC, Sultan C. A new recombinant cell bioassay for ultrasensitive determination of serum estrogenic bioactivity in children. J Clin Endocrinol Metab. 2002;87(2):791-797. doi: 10.1210/jc.87.2.791.
27. Aksglaede L, Juul A, Leffers H, Skakkebæk NE, Andersson AM. The sensitivity of the child to sex steroids: Possible impact of exogenous estrogens. Hum Reprod Update. 2006;12(4):341-349. doi: 10.1093/humupd/dml018.
28. Abd El-Meseeh NA, El-Shaarawy EAA, AlDomairy AF, Sehly RAA. Changes in rat testis morphology and androgen receptor expression around the age of puberty. Ann Anat. 2016;205:37-44. doi: 10.1016/j.aanat.2016.01.003.
29. Larmore KA, O’Connor D, Sherman TI, Funanage VL, Hassink SG, Klein KO. Leptin and estradiol as related to change in pubertal status and body weight. Med Sci Monit. 2002;8(3):CR206-CR210. doi:2292 [pii].
30. Klein KO, Baron J, Colli MJ, Mcdonnell DP, Cutler GB. Estrogen Levels in Childhood Determined by an Ultrasensitive Recombinant Cell Bioassay. 1994;94(6):2475-2480.
31. Hall JE. Endocrinology of the Menopause. Endocrinol Metab Clin North Am. 2015;44(3):485-496. doi: 10.1016/j.ecl.2015.05.010.
32. Buck Louis GM, Gray LE, Marcus M, Ojeda SR, Pescovitz OH, Witchel SF, et al. Environmental Factors and Puberty Timing: Expert Panel Research Needs. Pediatrics. 2008;121(Suppl 3):S192-S207. doi: 10.1542/peds.1813E.
33. Atwood CS, Meethal SV. The spatiotemporal hormonal orchestration of human folliculogenesis, early embryogenesis and blastocyst implantation. Mol Cell Endocrinol. 2016;430:33-48. doi: 10.1016/j.mce.2016.03.039.
34. Landázuri P, Granobles C, Loango N. Gender Differences in Serum Angiotensin-Converting Enzyme Activity and Blood Pressure in Children: an Observational Study. Arq Bras Cardiol. 2008;6(91):352- 357.
35. Gaete X, Codner E. Adelanto de la pubertad en Chile y el mundo. Rev Chil pediatría. 2006;77(5):456- 465. doi: 10.4067/S0370-41062006000500002.
36. Mompeón A, Lázaro-Franco M, Bueno-Betí C, Pérez-Cremades D, Vidal-Gómez X, Monsalve E, et al. Estradiol, acting through ERα, induces endothelial non-classic renin-angiotensin system increasing angiotensin 1-7 production. Mol Cell Endocrinol. 2016;422:1-8. doi: 10.1016/j.mce.2015.11.004.
37. Curtis KS. Estradiol and osmolality: Behavioral responses and central pathways. Physiol Behav. 2015;152(Pt B):422-430. doi: 10.1016/j.physbeh.2015.06.017.
38. Kamper M, Manns CC, Plieschnig JA, Schneider WJ, Ivessa NE, Hermann M. Estrogen enhances secretion of apolipoprotein B-100 containing lipoproteins by BeWo cells. Biochimie. 2015;112:121-128. doi: 10.1016/j.biochi.2015.03.002.
39. Palmeira AC, Leal AA de F, Ramos N de MN, Neto J de AF, Simoes MO da S, Medeiros CCM. Lipoprotein (a) and cardiovascular risk factors in children and adolescents. Rev Paul Pediatr. 2013;31(4):531-537. doi: 10.1590/S0103-05822013000400017.
40. Ohta T, Hattori S, Murakami M, Nishiyama S, Matsuda I. Age- and Sex-related Differences inLipoproteins Containing Apoprotein A-I. Arteriosclerosis Thromb Vasc Biol. 1989;9:90-95. doi: 10.1161/01.ATV.9.1.90.
41. Pelegrini A, Glaner MF, Petroski EL. Association between anthropometric indicators and serum lipid profile in adolescents. Hum Mov. 2012;13(3):242-246. doi: 10.2478/v10038-012-0028-z.
42. Persson L, Henriksson P, Westerlund E, Hovatta O, Angelin B, Rudling M. Endogenous estrogens lower plasma PCSK9 and LDL cholesterol but not Lp(a) or bile acid synthesis in women. Arterioscler Thromb Vasc Biol. 2012;32(3):810-814. doi: 10.1161/ATVBAHA.111.242461.
43. Hussain Y, Ding Q, Connelly PW, Brunt JH, Ban MR, McIntyre AD, et al. G-protein estrogen receptor as a regulator of low-density lipoprotein cholesterol metabolism: Cellular and population genetic studies. Arterioscler Thromb Vasc Biol. 2015;35(1):213-221. doi: 10.1161/ATVBAHA.114.304326.
44. Simoncini T, Mannella P, Fornari L, Caruso A, Willis MY, Garibaldi S, et al. Differential signal transduction of progesterone and medroxyprogesterone acetate in human endothelial cells. Endocrinology. 2004;145(12):5745-5756. doi: 10.1210/en.2004-0510.
45. Urbina EM, McCoy CE, Gao Z, Khoury PR, Shah AS, Dolan LM, et al. Lipoprotein particle number and size predict vascular structure and function better than traditional lipids in adolescents and young adults. J Clin Lipidol. 2017;11(4):1023-31. doi: 10.1016/j.jacl.2017.05.011.
46. Zavratnik A, Prezelj J, Kocijancic A, Marc J. Exonic, but not intronic polymorphisms of ESR1 gene might influence the hypolipemic effect of raloxifene. J Steroid Biochem Mol Biol. 2007;104(1-2):22-26. doi: 10.1016/j.jsbmb.2006.10.009.
47. Almeida S, Fiegenbaum M, de Andrade FM, Osório-Wender MC, Hutz MH. ESR1 and APOE gene polymorphisms, serum lipids, and hormonal replacement therapy. Maturitas. 2006;54(2):119-126.doi: 10.1016/j.maturitas.2005.09.009.
48. Klos KLE, Boerwinkle E, Ferrell RE, Turner ST, Morrison AC. ESR1 polymorphism is associated with plasma lipid and apolipoprotein levels in Caucasians of the Rochester Family Heart Study. J Lipid Res. 2008;49:1701-1706. doi: 10.1194/jlr.M700490-JLR2
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