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Acromegaly

内分泌

关键词内分泌 疾病 激素紊乱

词汇介绍

拓展阅读

解析

acromegaly   英/,ækrə(ʊ)'megəlɪ/   美/,ækrə'mɛgəli/

释    义   n. [内科] 肢端肥大症

例    句   Human adults given growth hormone have suffered from acromegaly( excess bone growth) and carpal tunnel syndrome. 成年人给予生长激素,则会造成末端肥大(头过度生长)及腕管综合症。

概述

肢端肥大症是一种激素紊乱,主要是由于体内过多的生长激素(GH)引起的。垂体是大脑中的小腺体,会产生GH,在肢端肥大症中,垂体产生过量的GH,通常,过量的GH来自垂体上的良性或非癌性肿瘤,这些良性肿瘤称为腺瘤。肢端肥大症最严重的后果是患2型糖尿病、高血压、心血管疾病和关节炎的风险增加。肢端肥大症患者的结肠息肉风险也增加,如果不切除,可能发展为结肠癌。临床表现肢端肥大症反映出其最常见的症状之一即手脚的异常生长。手和脚肿胀通常是早期特征,患者注意到戒指或鞋子的尺寸,特别是鞋子的宽度发生了变化。骨骼

Fibroblast activation protein is a GH target: A prospective study of patients with acromegaly before and after treatment复制标题

成纤维细胞活化蛋白是GH的靶点: 肢端肥大症患者治疗前后的前瞻性研究

发表时间:2019-09-23

影响因子:5.6

作者: Mai C Arlien-Soborg

期刊:J Clin Endocrinol Metab

Fibroblast growth factor 21 (FGF21) is a circulating hormone predominantly secreted from the liver with pleiotropic effects on substrate metabolism. The FGF21 receptor (FGFR) is expressed in numerous tissues and its activation by FGF21 depends on binding to β-Klotho, which is a transmembrane cofactor. The activity of circulating FGF21 is also regulated by fibroblast activation protein (FAP), a protease that cleaves and inactivates circulating FGF21. Data in mice show that FGF21 induces weight loss, increases energy expenditure (EE), improves insulin sensitivity in muscle, liver and fat, and stimulates lipolysis. Administration of FGF21 analogues in humans induces weight loss and favourable changes in plasma lipids, increases adiponectin levels and reduces intrahepatic lipid (IHL) deposition. However, endogenous serum FGF21 levels are elevated in obese human subjects and in patients with type 2 diabetes, indicating resistance to its actions. In addition, FGF21 transgenic mice are small and live longer, which are linked to hepatic growth hormone (GH) resistance and ensuing low IGF-I levels. At the same time, GH-induced stimulation of hepatic FGF21 expression feedback inhibits GH signalling and action via several mechanisms. Experimental data on the interaction between FGF21 and GH/IGF-I in human subjects, on the other hand, are sparse, but prolonged GH administration (>3 weeks) increases serum FGF21 levels in healthy subjects. It is unknown if FAP levels or activity are influenced by GH, but it is noteworthy that collagens are recognized FAP substrates in as much as GH is a very powerful stimulator of collagen turnover in human subjects. Acromegaly, which is caused by a GH-producing pituitary adenoma, is characterized by elevated EE, lipolysis, insulin resistance, and increased collagen turnover. In the present prospective study, we measured circulating components of FGF21 including FAP in patients with acromegaly before and after disease control. Potential biomarkers of FGF21 action, including expression of putative FGF21-regulated genes in adipose tissue, were recorded together with biomarkers of collagen turnover as potential FAP substrates. The most prominent finding was that FAP was strongly associated with both biochemical disease activity and collagen turnover.

译文

成纤维细胞生长因子21(FGF21)是一种主要从肝脏分泌的循环激素,对底物代谢具有多效作用。 FGF21受体(FGFR)在许多组织中表达,其被FGF21激活取决于与跨膜辅因子β-Klotho的结合。循环FGF21的活性也受成纤维细胞活化蛋白(FAP)的调节,FAP是一种蛋白酶,可裂解并灭活循环FGF21。小鼠中的数据表明,FGF21引起体重减轻,增加能量消耗(EE),改善肌肉,肝脏和脂肪中的胰岛素敏感性,并刺激脂肪分解。在人体内施用FGF21类似物可引起体重减轻和血浆脂质的有利变化,增加脂联素水平并减少肝内脂质(IHL)沉积。然而,在肥胖的人类受试者和患有2型糖尿病的患者中,内源性血清FGF21水平升高,表明对其作用有抗性。此外,FGF21转基因小鼠体积小,寿命更长,这与肝生长激素(GH)耐药性和随之而来的低IGF-I水平有关。同时,GH诱导的肝FGF21表达反馈刺激通过多种机制抑制GH信号传导和作用。另一方面,有关人类受试者中FGF21与GH / IGF-1之间相互作用的实验数据很少,但是长期服用GH(> 3周)会增加健康受试者的血清FGF21水平。尚不清楚FAP的水平或活性是否受GH影响,但值得注意的是,与GH一样,胶原蛋白也是FAP的底物,是人类受试者胶原蛋白更新的非常有力的刺激剂。肢端肥大症是由产生GH的垂体腺瘤引起的,其特征是EE升高,脂解作用,胰岛素抵抗和胶原蛋白更新增加。在本前瞻性研究中,我们在疾病控制前后对肢端肥大症患者的FGF21循环成分(包括FAP)进行了测量。记录了FGF21作用的潜在生物标志物,包括在脂肪组织中表达的公认的FGF21调控基因,以及作为潜在FAP底物的胶原蛋白更新生物标志物。最突出的发现是FAP与生化疾病活动和胶原蛋白更新密切相关。