Fedorczak Anna, Kowalik Dorota, Kopciuch Justyna, Głowacka Ewa, Mikołajczyk Katarzyna, Tkaczyk Marcin, Lewiński Andrzej, Stawerska Renata
Department of Endocrinology and Metabolic Diseases, Polish Mother's Memorial Hospital-Research Institute, 93-338 Lodz, Poland.
Center of Medical Laboratory Diagnostics and Screening, Polish Mother's Memorial Hospital-Research Institute, 93-338 Lodz, Poland.
Biomedicines. 2024 Jun 27;12(7):1433. doi: 10.3390/biomedicines12071433.
Sirtuin 1 (SIRT1) inhibits growth hormone (GH) intracellular signaling for the insulin-like growth factor 1 (IGF-1) synthesis via the janus kinase (JAK)/signal transducer and activator of transcription proteins (STATs) pathway. The aim of this study was to compare SIRT1 concentrations in children with GH deficiency (GHD) and so-called idiopathic short stature (ISS, non-GH deficient), in order to determine the possible impact of changes in serum SIRT1 concentrations on the GH-IGF-1 axis. The study group included 100 short-stature children: 38 with GHD and 62 with ISS (maxGH in two stimulation tests <10 and ≥10 ng/mL, respectively). The control group consisted of 47 healthy, normal-height children. For each child, the concentrations of SIRT1, IGF-1 and insulin-like growth factor-binding protein 3 (IGFBP-3) were determined and the IGF-1/IGFBP-3 molar ratio was calculated. The level of SIRT1 was significantly higher in both groups of short children than in the controls ( < 0.0001), but there were no differences between GHD and ISS (mean ± SD: 0.89 ± 0.45 for ISS; 1.24 ± 0, 86 for GHD; and 0.29 ± 0.21 for controls). A significant negative correlation was found between SIRT1 and height standard deviation score (SDS), IGF-1 and IGF-1/IGFBP-3, but not between SIRT1 and maxGH. Elevated SIRT1 levels may serve as one of the mechanisms through which the secretion of IGF-1 is reduced in children with short stature; however, further research is required to confirm this issue.
沉默调节蛋白1(SIRT1)通过Janus激酶(JAK)/信号转导及转录激活蛋白(STATs)途径抑制生长激素(GH)的细胞内信号传导,以合成胰岛素样生长因子1(IGF-1)。本研究的目的是比较生长激素缺乏症(GHD)儿童和所谓的特发性矮小症(ISS,非生长激素缺乏)儿童的SIRT1浓度,以确定血清SIRT1浓度变化对GH-IGF-1轴的可能影响。研究组包括100名身材矮小儿童:38名患有GHD,62名患有ISS(两次刺激试验中的最大生长激素分别<10和≥10 ng/mL)。对照组由47名健康、身高正常的儿童组成。测定每个儿童的SIRT1、IGF-1和胰岛素样生长因子结合蛋白3(IGFBP-3)浓度,并计算IGF-1/IGFBP-3摩尔比。两组身材矮小儿童的SIRT1水平均显著高于对照组(<0.0001),但GHD组和ISS组之间无差异(均值±标准差:ISS组为0.89±0.45;GHD组为1.24±0.86;对照组为0.29±0.21)。发现SIRT1与身高标准差评分(SDS)、IGF-1和IGF-1/IGFBP-3之间存在显著负相关,但SIRT1与最大生长激素之间无相关性。SIRT1水平升高可能是身材矮小儿童IGF-1分泌减少的机制之一;然而,需要进一步研究来证实这一问题。