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

Abstract

BackgroundTurner syndrome (TS) presents a high risk of congenital heart defects and may predispose to both obesity and related metabolic complications. Hence the search for new markers as potential early predictors of the metabolic syndrome (MetS) and cardiovascular diseases appears warranted.ObjectiveTo assess 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) in non-MetS TS girls not treated with growth hormone (GH) vs. healthy short stature girls, and to assess the connection with basic metabolic parameters.MethodThe concentrations of circulating MMP-1, MMP-2, MMP-9, BDNF, GDNF and VEGF were measured in 12 patients with TS not treated with growth hormone. The control group was composed of 17 girls with non-pathologic short stature. The patients’ clinical and biochemical phenotypes were determined by weight, height, total cholesterol, HDL cholesterol, triglycerides, glucose, aminotransferases, IGF1, TSH and fT4.ResultsThere were no differences in mean age, weight, BMI Z-Score, or hSDS between the studied group and the controls; however, they differed in baseline values of ALT (18.2 ± 4.2 vs. 14.2 ± 4.1, p= 0.02), BDNF [29951.5 (26176.9 – 41271.9) vs. 23131.7 (18392.4 – 28313.3), p=0.01] and MMP-2 [91.8 (71.7 – 111.0) vs. 143.6 (123.7 - 244.5), p< 0.001]. BDNF correlated with ALT activity (r = 0.56 p = 0.002) and BMI Z-score (r = 0.38 p = 0.042), while MMP-2 correlated with HDL concentration (r = 0.48 p = 0.029) in all the patients. The analysis of the study group alone revealed significant positive correlations between MMP-9 and TSH (r = 0.74 p = 0.036), BDNF and both ALT (r = 0.73 p = 0.038) and TSH (r = 0.85 p = 0.008), and a negative correlation between MMP-1 and fT4 (r = -0.75 p = 0.032). The control group did not present any significant correlations.ConclusionThe higher concentrations of BDNF and lower of MMP-2 found in girls with TS without MetS compared to healthy girls with short stature, could have a major impact on the future “natural” development of the metabolic status. Our findings need further studies.

Effect of Growth Hormone Treatment on the Concentration of Selected Metabolic Markers in Girls With Turner Syndrome

“…According to some reports, the concentration of MMPs increases with age ( 46 ), so it is difficult to clearly compare our results with those of Rendeva et al. Unfortunately, we do not have any reports from studies on MMP-2 levels in patients with TS, other than our two previous studies ( 5 ) ( 6 ), which suggested lower MMP-2 plasma concentration in girls with TS before GH treatment than in healthy girls with short stature.…”

“…Moreover, MMP-2 and MMP-9 levels were elevated in patients with isolated systolic hypertension as compared to the control group ( 34 , 35 ). In our previous study, MMP-1 was significantly higher in the study group, with a significant positive correlation with Z-score BMI ( 5 ), while studies before GH treatment revealed lower concentrations of MMP-2 in girls with TS compared to healthy girls with short stature ( 6 ).…”

“…Most likely, some BDNF genotypes resulting from BDNF gene polymorphism can be recognized as a potential factor in the development of obesity and insulin resistance ( 14 , 15 ). Our previous studies revealed higher BDNF levels in girls with TS, both before the onset of GH therapy ( 5 ) as well as during treatment ( 6 ) compared to the control group. Interestingly, the assessment of BDNF concentration in adult TS patients by other authors confirms its higher concentration in patients with this syndrome ( 16 ).…”

“…Our previous study was performed on 17 patients with TS undergoing growth hormone (GH) therapy ( 5 ). Subsequently, we re-examined the markers concentration before the onset of GH therapy to exclude its potential influence ( 6 ).…”

“…BDNF, a member of the nerve growth factor family, is also involved in weight regulation and energy expenditure by reducing appetite ( 7 ). The concentration of BDNF correlates negatively with body weight ( 8 ) and age ( 9 ); therefore, it is believed to be an anti-aging factor ( 6 ). BDNF affects glucose and lipid metabolism and is also considered an anorexigenic factor ( 10 ).…”