{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:51:47Z","timestamp":1753890707625,"version":"3.41.2"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T00:00:00Z","timestamp":1655078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>As Turner syndrome (TS) predisposes to obesity and metabolic disorders, and their complications, such as cardiovascular diseases, are the main causes of shortened life expectancy in patients with TS, new metabolic markers that could serve as early predictors of dysmetabolic state are sought.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>Assessment of MMP-1 (matrix metalloproteinase-1), MMP-2 (matrix metalloproteinase-2), MMP-9 (matrix metallopeptidase-9), BDNF (brain-derived neurotrophic factor), GDNF (glial cell line-derived neurotrophic factor), and VEGF (vascular endothelial growth factor) before the onset of growth hormone (GH) therapy and then during GH treatment as well as markers assessment during GH medication in girls with TS to establish marker stability and repeatability, and the impact of GH on markers concentration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>The concentrations of circulating MMP-1, MMP-2, MMP-9, BDNF, GDNF, and VEGF were measured in nine girls with TS before the onset of GH therapy and then after at least 3 months of treatment period. Subsequently, markers concentration was determined in 17 girls during GH medication, with the first determination after at least a 3-month treatment period. The patients\u2019 clinical and biochemical phenotypes were determined by weight, height, BMI, total cholesterol, HDL cholesterol, triglycerides, and glucose concentration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Comparison of markers concentration revealed a significantly higher concentration of MMP-2 in patients undergoing GH treatment (132.1 \u00b1 42.05) than before the onset of therapy (105.0 \u00b1 45.5, p=0.045). The values of the first measurement of VEGF in girls with TS undergoing GH therapy were significantly higher than those during the second measurement (30.9 \u00b1 33.4 vs. 12.5 \u00b1 11.7, p=0.029). There were no statistically significant differences between the measurements of the remaining markers concentration at any stage of the analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Increase in MMP-2 concentration is visible during GH therapy in comparison to the pre-GH period in girls with TS which demands confirmation in subsequent tests. The role of VEGF requires further studies in the context of carbohydrate-lipid disturbances in girls with TS and its association with GH treatment.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.818735","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T04:19:33Z","timestamp":1655093973000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of Growth Hormone Treatment on the Concentration of Selected Metabolic Markers in Girls With Turner Syndrome"],"prefix":"10.3389","volume":"13","author":[{"given":"Ewa","family":"B\u0142aszczyk","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jakub","family":"Gawlik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"Gieburowska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Tokarska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma\u0142gorzata","family":"Kimsa-Furdzik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grzegorz","family":"Hibner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Francuz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aneta","family":"Gawlik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1210\/er.2008-0024","article-title":"The Metabolic Syndrome","volume":"29","author":"Cornier","year":"2008","journal-title":"Endocr Rev"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-1939","article-title":"Excess Visceral and Hepatic Adipose Tissue in Turner Syndrome Determined by Magnetic Resonance Imaging: Estrogen Deficiency Associated With Hepatic Adipose Content","volume":"90","author":"Ostberg","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"B3","doi-asserted-by":"publisher","first-page":"G1","DOI":"10.1530\/EJE-17-0430","article-title":"Clinical Practice Guidelines for the Care of Girls and Women With Turner Syndrome: Proceedings From the 2016 Cincinnati International Turner Syndrome Meeting","volume":"177","author":"Gravholt","year":"2017","journal-title":"Eur J Endocrinol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra030360","article-title":"Turner\u2019s Syndrome","volume":"351","author":"Sybert","year":"2004","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2018\/9715790","article-title":"Selected Metabolic Markers in Girls With Turner Syndrome: A Pilot Study","volume":"2018","author":"B\u0142aszczyk","year":"2018","journal-title":"Int J Endocrinol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/FENDO.2021.722199","article-title":"Brain-Derived Neurotropic Factor, Vascular Endothelial Growth Factor and Matrix Metalloproteinases as Markers of Metabolic Status in Non-Growth Hormone-Treated Girls With Turner Syndrome","author":"B\u0142aszczyk","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(95)90045-4","article-title":"Characteristics of BDNF-Induced Weight Loss","volume":"131","author":"Pelleymounter","year":"1995","journal-title":"Exp Neurol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2004.03.002","article-title":"The Impact of Age, Weight and Gender on BDNF Levels in Human Platelets and Plasma","volume":"26","author":"Lommatzsch","year":"2005","journal-title":"Neurobiol Aging"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2006.06.011","article-title":"Serum Neurotrophins\u2013a Study on the Time Course and Influencing Factors in a Large Old Age Sample","volume":"28","author":"Ziegenhorn","year":"2007","journal-title":"Neurobiol Aging"},{"key":"B10","first-page":"79","article-title":"NGF and BDNF: From Nerves to Adipose Tissue, From Neurokines to Metabokines","volume":"44","author":"Chaldakov","year":"2009","journal-title":"Riv Psichiatr"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1097\/JSM.0000000000000082","article-title":"Influence of Aerobic Training and Detraining on Serum BDNF, Insulin Resistance, and Metabolic Risk Factors in Middle-Aged Men Diagnosed With Metabolic Syndrome","volume":"24","author":"Damirchi","year":"2014","journal-title":"Clin J Sport Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2005.08.055","article-title":"Metabolic Syndrome \u2013 Neurotrophic Hypothesis","volume":"66","author":"Hristova","year":"2006","journal-title":"Med Hypotheses"},{"key":"B13","first-page":"HY19","article-title":"Metabotrophic Potential of Neurotrophins: Implication in Obesity and Related Diseases","volume":"9","author":"Chaldakov","year":"2003","journal-title":"Med Sci Monit Int Med J Exp Clin Res"},{"key":"B14","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/ng.274","article-title":"Genome-Wide Association Yields New Sequence Variants at Seven Loci That Associate With Measures of Obesity","volume":"41","author":"Thorleifsson","year":"2009","journal-title":"Nat Genet"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/bdi.12294","article-title":"The Brain-Derived Neurotrophic Factor (BDNF) Val66Met Polymorphism Is Associated With Increased Body Mass Index and Insulin Resistance Measures in Bipolar Disorder and Schizophrenia","volume":"17","author":"Bonaccorso","year":"2015","journal-title":"Bipolar Disord"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3109\/09513590.2013.871513","article-title":"Brain-Derived Neurotrophic Factor Plasma Levels in Patients With Turner Syndrome","volume":"30","author":"Czyzyk","year":"2014","journal-title":"Gynecol Endocrinol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/373339a0","article-title":"Mesencephalic Dopaminergic Neurons Protected by GDNF From Axotomy-Induced Degeneration in the Adult Brain","volume":"373","author":"Beck","year":"1995","journal-title":"Nature"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2136","article-title":"Absolute Requirement of GDNF for Adult Catecholaminergic Neuron Survival","volume":"11","author":"Pascual","year":"2008","journal-title":"Nat Neurosci"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00364.2013","article-title":"Glial Cell Line-Derived Neurotrophic Factor Protects Against High-Fat Diet-Induced Obesity","volume":"306","author":"Mwangi","year":"2014","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1212\/WNL.60.1.69","article-title":"Randomized, Double-Blind Trial of Glial Cell Line-Derived Neurotrophic Factor (GDNF) in PD","volume":"60","author":"Nutt","year":"2003","journal-title":"Neurology"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.03.087","article-title":"Biology of Vascular Endothelial Growth Factors","volume":"580","author":"Roy","year":"2006","journal-title":"FEBS Lett"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.2337\/db08-1098","article-title":"Reduced Adipose Tissue Oxygenation in Human Obesity: Evidence for Rarefaction, Macrophage Chemotaxis, and Inflammation Without an Angiogenic Response","volume":"58","author":"Pasarica","year":"2009","journal-title":"Diabetes"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1164\/rccm200308-1200OC","article-title":"Hypoxia Causes Glucose Intolerance in Humans","volume":"169","author":"Oltmanns","year":"2004","journal-title":"Am J Respir Crit Care Med"},{"key":"B24","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1079\/BJN20041213","article-title":"Adipokines: Inflammation and the Pleiotropic Role of White Adipose Tissue","volume":"92","author":"Trayhurn","year":"2004","journal-title":"Br J Nutr"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.2337\/db11-0832","article-title":"Adipose Tissue Overexpression of Vascular Endothelial Growth Factor Protects Against Diet-Induced Obesity and Insulin Resistance","volume":"61","author":"Elias","year":"2012","journal-title":"Diabetes"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012610","article-title":"Evidence for a Relationship Between VEGF and BMI Independent of Insulin Sensitivity by Glucose Clamp Procedure in a Homogenous Group Healthy Young Men","volume":"5","author":"Loebig","year":"2010","journal-title":"PloS One"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0802987","article-title":"Angiogenic Factors are Elevated in Overweight and Obese Individuals","volume":"29","author":"Silha","year":"2005","journal-title":"Int J Obes"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2005.12.002","article-title":"Structure and Function of Matrix Metalloproteinases and TIMPs","volume":"69","author":"Nagase","year":"2006","journal-title":"Cardiovasc Res"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1101\/gad.815400","article-title":"Matrix Metalloproteinases: Effectors of Development and Normal Physiology","volume":"14","author":"Vu","year":"2000","journal-title":"Genes Dev"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvm007","article-title":"Angiogenesis and Obesity","volume":"78","author":"Lijnen","year":"2008","journal-title":"Cardiovasc Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1210\/en.2011-1026","article-title":"TLR4 Activation and IL-6-Mediated Cross Talk Between Adipocytes and Mononuclear Cells Synergistically Stimulate MMP-1 Expression","volume":"152","author":"Samuvel","year":"2011","journal-title":"Endocrinology"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.231\/JIM.0b013e318294e9da","article-title":"Gelatinases and Their Tissue Inhibitors in a Group of Subjects With Metabolic Syndrome","volume":"61","author":"Hopps","year":"2013","journal-title":"J Investig Med"},{"key":"B33","article-title":"The Association of Vascular Endothelial Growth Factor, Metalloproteinases and Their Tissue Inhibitors With Cardiovascular Risk Factors in the Metabolic Syndrome That MMP-2 May Have a Role in the Increased Cardiovascular Risk of MetS Patients","volume":"20","author":"Erman","year":"2016","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000151373.33830.41","article-title":"Matrix Metalloproteinase-9 (MMP-9), MMP-2, and Serum Elastase Activity Are Associated With Systolic Hypertension and Arterial Stiffness","volume":"25","author":"Yasmin","year":"2004","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-012-2356-7","article-title":"Effect of Metabolic Syndrome Risk Factors and MMP-2 Genetic Variations on Circulating MMP-2 Levels in Childhood Obesity","volume":"40","author":"Belo","year":"2013","journal-title":"Mol Biol Rep"},{"key":"B36","article-title":"Siatki Centylowe do Oceny Rozwoju Somatycznego Dzieic I M\u0142odzie\u017cy","author":"Palczewska","year":"1999","journal-title":"Warszawa: Polish Institute of Mother\u2019s and Child\u2019s Health"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1111\/j.2047-6310.2012.00064.x","article-title":"Extended International (IOTF) Body Mass Index Cut-Offs for Thinness, Overweight and Obesity","volume":"7","author":"Cole","year":"2012","journal-title":"Pediatr Obes"},{"key":"B38","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1136\/adc.44.235.291","article-title":"Variations in Pattern of Pubertal Changes in Girls","volume":"44","author":"Marshall","year":"1969","journal-title":"Arch Dis Child"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-5448.2003.t01-1-00022.x","article-title":"Evaluation of HOMA and QUICKI as Measures of Insulin Sensitivity in Prepubertal Children","volume":"4","author":"Cutfield","year":"2003","journal-title":"Pediatr Diabetes"},{"key":"B40","doi-asserted-by":"publisher","first-page":"S4","DOI":"10.1038\/ijo.2014.130","article-title":"Metabolic Syndrome in Young Children: Definitions and Results of the IDEFICS Study","volume":"38","author":"Ahrens","year":"2014","journal-title":"Int J Obes"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60958-1","article-title":"The Metabolic Syndrome in Children and Adolescents","volume":"369","author":"Zimmet","year":"2007","journal-title":"Lancet"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.31.21491","article-title":"Matrix Metalloproteinases","volume":"274","author":"Nagase","year":"1999","journal-title":"J Biol Chem"},{"key":"B43","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/BS.APHA.2017.08.002","article-title":"Matrix Metalloproteinases, Vascular Remodeling, and Vascular Disease","volume":"81","author":"Wang","year":"2018","journal-title":"Adv Pharmacol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/J.BMC.2007.01.011","article-title":"Matrix Metalloproteinases (MMPs): Chemical\u2013biological Functions and (Q)SARs","volume":"15","author":"Verma","year":"2007","journal-title":"Bioorg Med Chem"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000129763.51060.77","article-title":"Growth Hormone Replacement Decreases Plasma Levels of Matrix Metalloproteinases (2 and 9) and Vascular Endothelial Growth Factor in Growth Hormone\u2013Deficient Individuals","volume":"109","author":"Randeva","year":"2004","journal-title":"Circulation"},{"key":"B46","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1002\/AGM2.12099","article-title":"Proinflammation, Profibrosis, and Arterial Aging","volume":"3","author":"Wang","year":"2020","journal-title":"Aging Med"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1159\/000087451","article-title":"Angiotensin II Stimulates Matrix Metalloproteinase Secretion in Human Vascular Smooth Muscle Cells via Nuclear Factor-\u03bab and Activator Protein 1 in a Redox-Sensitive Manner","volume":"42","author":"Browatzki","year":"2005","journal-title":"J Vasc Res"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(03)00140-0","article-title":"High Glucose Alters Matrix Metalloproteinase Expression in Two Key Vascular Cells: Potential Impact on Atherosclerosis in Diabetes","volume":"168","author":"Death","year":"2003","journal-title":"Atherosclerosis"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-8-50","article-title":"MMP-1 Serum Levels Predict Coronary Atherosclerosis in Humans","volume":"8","author":"Lehrke","year":"2009","journal-title":"Cardiovasc Diabetol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/J.AMJHYPER.2004.06.023","article-title":"Tissue Inhibitor of Metalloproteinase-1 and Matrix Metalloproteinase-9 Levels in Patients With Hypertensionrelationship to Tissue Doppler Indices of Diastolic Relaxation","volume":"17","author":"Tayebjee","year":"2004","journal-title":"Am J Hypertens"},{"key":"B51","doi-asserted-by":"publisher","first-page":"2993","DOI":"10.1210\/JC.2009-2623","article-title":"Matrix Metalloproteinase-9 Is Increased in Obese Subjects and Decreases in Response to Pioglitazone","volume":"95","author":"Unal","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2005.02.030","article-title":"Potential Involvement of Vascular Endothelial Growth Factor in Pathophysiology of Turner Syndrome","volume":"65","author":"Brandenburg","year":"2005","journal-title":"Med Hypotheses"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.83.8.832","article-title":"Vascular Endothelial Growth Factor Upregulates the Expression of Matrix Metalloproteinases in Vascular Smooth Muscle Cells","volume":"83","author":"Wang","year":"1998","journal-title":"Circ Res"},{"key":"B54","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1111\/J.1469-1809.2006.00298.X","article-title":"Heritability for Plasma VEGF Concentration in the Stanislas Family Study","volume":"71","author":"Berrahmoune","year":"2007","journal-title":"Ann Hum Genet"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1046\/J.1365-2265.1999.00671.X","article-title":"Endothelial Dysfunction in Hypopituitary Adults With Growth Hormone Deficiency","volume":"50","author":"Evans","year":"1999","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1186\/1687-9856-2012-5","article-title":"Impaired Endothelial Function in Pediatric Patients With Turner Syndrome and Healthy Controls: A Case-Control Study","volume":"2012","author":"O\u2019Gorman","year":"2012","journal-title":"Int J Pediatr Endocrinol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1210\/JCEM.84.2.5456","article-title":"Growth Hormone (GH) Treatment Reverses Early Atherosclerotic Changes in GH-Deficient Adults","volume":"84","author":"Pfeifer","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"key":"B58","doi-asserted-by":"publisher","first-page":"10091","DOI":"10.1038\/S41598-018-28375-0","article-title":"Assessment of the Key Regulatory Genes and Their Interologs for Turner Syndrome Employing Network Approach","volume":"8","author":"Farooqui","year":"2018","journal-title":"Sci Rep"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.818735\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T04:19:40Z","timestamp":1655093980000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.818735\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,13]]},"references-count":58,"alternative-id":["10.3389\/fendo.2022.818735"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.818735","relation":{},"ISSN":["1664-2392"],"issn-type":[{"type":"electronic","value":"1664-2392"}],"subject":[],"published":{"date-parts":[[2022,6,13]]},"article-number":"818735"}}