Growth Hormone & Igf Research最新文献

Corrigendum to “Pharmacodynamics, pharmacokinetics, and toxicology of Fc-growth hormone fusion protein in macaques”

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2025-04-22 DOI: 10.1016/j.ghir.2025.101649

Han Liu , Binghuai Peng , Baisong Zhou , Yu Zhang , Yunnan Liu , Yulin Liu , Ruixin Sun , Zhuonan Li , Qiumei Zhu , Lu Yu , Ruili Fu , Qiong Wang , Jinghui Liu , Chunying Pang

引用次数: 0

Pharmacodynamics, pharmacokinetics, and toxicology of Fc-growth hormone fusion protein in macaques

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2025-03-19 DOI: 10.1016/j.ghir.2025.101648

Han Liu, Binghuai Peng, Baisong Zhou, Yu Zhang, Yunnan Liu, Yulin Liu, Ruixin Sun, Zhuonan Li, Qiumei Zhu, Lu Yu, Ruili Fu, Qiong Wang, Jinghui Liu, Chunying Pang

Purpose

Growth hormone (GH) therapy for GH deficiency is used to treat multiple conditions. However, the short half-life of GH necessitates frequent dosing, which limits patient adherence. Fc fusion proteins, created by binding an active peptide to the Fc portion of IgG, are known to prolong the plasma half-life of the peptide. Pharmacodynamics and pharmacokinetics of Fc-GH in rats have been reported; however, studies in primate models are lacking. Therefore, in this study, we aimed to investigate the pharmacodynamics, pharmacokinetics, and toxicology of Fc-GH in rhesus and crab-eating macaques.

Methods

In rhesus macaques, Fc-GH was injected subcutaneously at 0.8, 1.6, and 3.2 mg/kg and intravenously at 1.6 mg/kg. The 1.6 mg/kg subcutaneous dose was administered five times, once every 7 days; other doses were administered as single injections for pharmacodynamic and pharmacokinetic assessments. In crab-eating macaques, potential toxicity was evaluated after single subcutaneous injections at 30, 45, and 62.5 mg/kg and repeated injections at 3, 10, and 30 mg/kg once every 7 days, followed by an 8-week recovery.

Results

No adverse events were observed following Fc-GH administrations. Fc-GH achieved C_max slowly after subcutaneous administration and rapidly after intravenous administration, with plasma levels being maintained over time. In rhesus macaques, the half-life increased dose-dependently: 23.72 ± 2.17 h (0.8 mg/kg), 49.44 ± 14.77 h (1.6 mg/kg), and 76.07 ± 13.19 h (3.2 mg/kg). After five injections of 1.6 mg/kg, the half-life of Fc-GH was 60.42 ± 18.29 h. Insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) levels significantly increased and remained elevated for 28–42 days after Fc-GH injections. In crab-eating macaques, no Fc-GH accumulation was observed. The maximum tolerated single subcutaneous dose was 62.5 mg/kg; no adverse effects were observed at 30 mg/kg during repeated administration over 29 injections with an 8-week recovery.

Conclusions

Fc-GH demonstrated favorable pharmacokinetics and pharmacodynamics in macaques, significantly extending the half-life and enhancing IGF-1 and IGFBP-3 levels without adverse effects. These findings suggest Fc-GH as a promising long-acting GH therapy that could improve patient adherence.

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引用次数: 0

Picropodophyllotoxin alters EMT in neuroblastoma via inhibition of surface receptors IFG1R and ALK

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2025-02-20 DOI: 10.1016/j.ghir.2025.101638

Poonam Bhagriya , Afridi Shaikh , Hetal Roy

Neuroblastoma (NB) is a type of paediatric cancer that originates from embryonic sympathoadrenal cells. Despite its paediatric origin, NB is mostly treated with strategy of non-small cell lung cancer like adults due to lack of specific therapeutic approach. To improve treatment outcome for NB patients, developing drugs that specifically target the genetic mutations or molecular pathways involved in neuroblastoma is necessary. Overexpression of the insulin-like growth factor 1 receptor (IGF1R) has been linked to various malignancies, including paediatric cancers. We hypothesized that inhibiting IGF1R with ALK (NB specific mutation) by phytochemical compound could effectively treat NB while avoiding undesirable cytotoxic effects. We evaluated the efficacy of Picropodophyllotoxin (PPP) as IGF1R inhibitor, for treatment of NB. The IC₅₀ value of PPP on SH-SY5Y, NB cells after 24 h of treatment was found to be 0.501 μM. Molecular docking studies revealed that PPP had a binding score of −7.5 kcal/mol with IGF1R and − 8.8 kcal/mol with ALK. This suggests that PPP not only binds to and inhibits IGF1R but also has a strong affinity for ALK. Gene expression studies, densitometric analysis, scratch assays, and AO/EtBr differential staining were used to evaluate the efficacy of PPP in NB cells. Transcript expression and densitometric analysis revealed that PPP could downregulate IGF1R and ALK in NB cells. Downregulation of SNAIL, a mesenchymal marker, and upregulation of E-cadherin, an epithelial marker, indicated a mesenchymal to epithelial transition in NB cells, suggesting that PPP treatment inhibited NB cell migration and proliferation. This was further supported by scratch assay results in our study. Furthermore, gene expression analysis of p53, BAX and BCL2 indicated that PPP induces apoptosis in NB cells. AO/EtBr differential staining revealed apoptotic phenomena in NB cells after 24 h of PPP treatment. Although further research is needed to explore the receptor targeting approach using PPP for IGF1R and ALK inhibition.

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引用次数: 0

Cellular senescence and PAPP-A

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2025-01-23 DOI: 10.1016/j.ghir.2025.101637

Cheryl A. Conover

Cellular senescence and its accompanying secretome have major impact on growth and aging of mammalian organisms. A novel protease, PAPP-A, regulates the bioavailability of an important growth factor, insulin-like growth factor (IGF)-I, and has major impact on growth and aging. This short review will explore a new perspective of cellular senescence and PAPP-A.

引用次数: 0

Identification and differentiation of somapacitan, a long-acting growth hormone derivative, and recombinant human growth hormone in equine plasma by LC-HRMS for doping control purpose hplc - hrms鉴别马血浆中长效生长激素衍生物somapacitan和重组人生长激素

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2024-11-10 DOI: 10.1016/j.ghir.2024.101628

Yoshibumi Shimizu, Michiko Sugai-Bannai, Kazunobu Saito, Misato Hirano-Kodaira, Gary Ngai-Wa Leung

Somapacitan, a long-acting growth hormone derivative, and recombinant human growth hormone (rhGH) are protein-based drugs generally used to treat growth disorders and GH deficiency in humans. Due to their potential to enhance the horse performance, the use of these drugs is prohibited at-all-times by the International Federation of Horseracing Authorities for horseracing and the Fédération Equestre Internationale for equestrian sports. In this study, we developed a test method for the identification and differentiation of somapacitan and rhGH in equine plasma by using liquid chromatography high-resolution mass spectrometry (LC–HRMS). The method involved C4 solid-phase extraction after ammonium sulfate precipitation, followed by chloroform/methanol precipitation, trypsin digestion, and analysis by LC-HRMS. The discriminative identification of somapacitan and rhGH was successfully achieved through the detection of their respective unique T10 peptide fragments. Noteworthy, the T10 peptide fragment of somapacitan was detected with its side chain structure remaining intact. The limit of identification (confirmation) (LOI) was determined to be 5 ng/mL for somapacitan and 2 ng/mL for rhGH in equine plasma, while the limit of detection (LOD) was 5 ng/mL for somapacitan and 1 ng/mL for rhGH. Furthermore, using the peptide fragments T1, T8, and T9 (which are shared between somapacitan and rhGH), the presence of somapacitan in equine plasma could be confirmed with higher sensitivity, achieving down to LOIs of 2 ng/mL and LODs of 1 ng/mL. The method was validated with respect to specificity, identification capability, robustness, precision, and reproducibility, paving the way for the analysis of post-administration samples from our already planned administration trials and future potential positive cases.

Somapacitan是一种长效生长激素衍生物，重组人生长激素（rhGH）是一种基于蛋白质的药物，通常用于治疗人类生长障碍和生长激素缺乏症。由于这些药物有可能提高马匹的表现，国际赛马当局联合会和国际马术协会在任何时候都禁止使用这些药物。本研究建立了马血浆中somapacitan和rhGH的液相色谱-高分辨率质谱（LC-HRMS）鉴别鉴别方法。方法采用硫酸铵沉淀后C4固相萃取，氯仿/甲醇沉淀，胰蛋白酶消化，LC-HRMS分析。通过检测其各自独特的T10肽片段，成功实现了somapacitan和rhGH的鉴别鉴定。值得注意的是，somapacitan的T10肽片段被检测到，其侧链结构保持完整。马血浆中somapacitan的检出（确认）限为5 ng/mL， rhGH的检出限为2 ng/mL， somapacitan的检出限为5 ng/mL， rhGH的检出限为1 ng/mL。此外，利用somapacitan和rhGH共有的肽片段T1、T8和T9，可以以更高的灵敏度确认马血浆中somapacitan的存在，LOIs可低至2 ng/mL， LODs可达1 ng/mL。该方法在特异性、鉴定能力、稳健性、精确性和重复性方面得到了验证，为分析我们已经计划的给药试验和未来潜在阳性病例的给药后样本铺平了道路。

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引用次数: 0

Association of rs35767 polymorphism in the IGF1 gene with athletic performance in power and endurance sports: A meta-analysis IGF1 基因 rs35767 多态性与力量和耐力运动成绩的关系：荟萃分析

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2024-11-05 DOI: 10.1016/j.ghir.2024.101627

João Mendes , João Palma , Amândio Santos , Joana Ribeiro , Bárbara Oliveiros , Henriqueta Silva

Background

Sport performance is a multifactorial phenotype dependent on the interaction of multiple genetic and non-genetic factors. More than 200 polymorphisms have been associated with athletic performance. The single nucleotide polymorphism (SNP) rs35767, located in the regulatory region of the IGF1 gene, influences its expression and has been associated with sports-related phenotypes. We aimed to perform a meta-analysis to evaluate the association between the rs35767 polymorphism of the IGF1 gene and athletic performance in power and endurance sports.

Methods

Literature has been retrieved from PubMed, Web of Science, Scopus, Embase, and Sport Discus databases until October 2023. This study was designed according to the PRISMA statement. Different models were tested, and heterogeneity was evaluated.

Results

Three studies were included in this meta-analysis. Statistically significant differences were highlighted for the frequency of the minor allele when comparing all athletes and controls (p < 0.001; OR = 1.74; 95 % CI = 1.26–2.40), endurance athletes and controls (p = 0.016; OR = 1.87; 95 % CI = 1.12–3.1) and power sport athletes and controls (p = 0.007; OR = 1.62; 95 % CI = 1.14–2.31). No statistically significant difference was found between the power and endurance groups. According to data analysis, the recessive model is the most suitable genetic model.

Conclusions

This metanalysis supports the role of the minor allele of the rs35767 polymorphism of the IGF1 gene as favoring an athlete's performance in endurance and power sports.

背景：运动成绩是一种多因素表型，取决于多种遗传和非遗传因素的相互作用。有 200 多个多态性与运动成绩相关。位于 IGF1 基因调控区的单核苷酸多态性（SNP）rs35767 会影响 IGF1 基因的表达，并与运动相关表型有关。我们旨在进行一项荟萃分析，以评估 IGF1 基因 rs35767 多态性与力量和耐力运动的运动表现之间的关联：从 PubMed、Web of Science、Scopus、Embase 和 Sport Discus 数据库中检索了截至 2023 年 10 月的文献。本研究根据 PRISMA 声明进行设计。对不同的模型进行了测试，并对异质性进行了评估：本荟萃分析纳入了三项研究。在比较所有运动员和对照组时，发现小等位基因的频率存在统计学意义上的明显差异（p 结论：本荟萃分析支持小等位基因的作用：这项荟萃分析支持 IGF1 基因 rs35767 多态性的小等位基因有利于运动员在耐力和力量运动中的表现。

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引用次数: 0

The association between change in temporal muscle mass and treatment of acromegaly 颞部肌肉质量变化与肢端肥大症治疗之间的关联。

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2024-10-10 DOI: 10.1016/j.ghir.2024.101626

Serdar Sahin , Ahmet Oz , Burcu Saglamer , Cem Sulu , Ahmet Numan Demir , Lala Soltanova , Mustafa Duru , Serdar Arslan , Hande Mefkure Ozkaya , Osman Kizilkilic , Necmettin Tanriover , Pinar Kadioglu

Purpose

We aimed to evaluate the relationship between temporal muscle thickness and GH/IGF-1 elevation and the effect of acromegaly treatment on temporal muscle thickness.

Methods

Patients with acromegaly and healthy controls were included in the study. While laboratory parameters, clinical findings and temporal muscle thickness of acromegaly patients at the time of diagnosis and one year after treatment were evaluated, laboratory parameters and temporal muscle thickness of healthy controls were evaluated only during the period when they were included in the study. Temporal muscle thickness was measured using pituitary MRI. Temporal muscle thickness of patients with acromegaly was compared with healthy controls. We also evaluated how temporal muscle thickness changes with treatment in patients with acromegaly and the association between laboratory parameters and temporal muscle thickness.

Results

In patients with acromegaly, measurements of left, right, and mean temporal muscle thickness at the time of diagnosis were found to be significantly higher than those of healthy controls' measurements at the time of their inclusion in the study (p = 0.007, p = 0.014 and p = 0.018, respectively). However, no significant difference was found when comparing the temporal muscle thickness of the 1st year of acromegaly treatment with the temporal muscle thickness of healthy controls at the time of their inclusion in the study (p = 0.155, p = 0.189, p = 0.198, respectively). In addition, a significant decrease was detected in the left, right and mean temporal muscle thicknesses of patients with acromegaly before and after treatment. While the temporal muscle thickness at the time of diagnosis was thicker in patients with acromegaly receiving surgical + medical treatment than in patients receiving exclusively surgical treatment, statistical significance was only found in the left temporal muscle thickness (p = 0.042).

Conclusion

Temporal muscle thickness was found to be associated with treatment modalities in patients with acromegaly.

目的：我们旨在评估颞肌厚度与 GH/IGF-1 升高之间的关系，以及肢端肥大症治疗对颞肌厚度的影响：研究对象包括肢端肥大症患者和健康对照组。在对肢端肥大症患者诊断时和治疗一年后的实验室参数、临床表现和颞肌厚度进行评估的同时，仅在健康对照组参与研究期间对其实验室参数和颞肌厚度进行评估。颞肌厚度通过垂体磁共振成像进行测量。肢端肥大症患者的颞肌厚度与健康对照组进行了比较。我们还评估了肢端肥大症患者颞肌厚度随治疗的变化情况，以及实验室参数与颞肌厚度之间的关联：结果：发现肢端肥大症患者确诊时的左侧、右侧和平均颞肌厚度测量值明显高于健康对照组纳入研究时的测量值（分别为 p = 0.007、p = 0.014 和 p = 0.018）。然而，在将肢端肥大症治疗第一年的颞肌厚度与健康对照组纳入研究时的颞肌厚度进行比较时，并未发现明显差异（分别为 p = 0.155、p = 0.189 和 p = 0.198）。此外，肢端肥大症患者在治疗前后的左侧、右侧和平均颞肌厚度均有明显下降。虽然接受手术+药物治疗的肢端肥大症患者在确诊时的颞肌厚度比只接受手术治疗的患者厚，但只有左侧颞肌厚度具有统计学意义（p = 0.042）：结论：颞肌厚度与肢端肥大症患者的治疗方式有关。

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引用次数: 0

Pregnancy-associated plasma protein-A (PAPP-A) and cardiovascular disease 妊娠相关血浆蛋白-A（PAPP-A）与心血管疾病。

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2024-10-09 DOI: 10.1016/j.ghir.2024.101625

Cheryl A. Conover

There is strong evidence that PAPP-A, a local regulator of insulin-like growth factor signaling through proteolytic cleavage of inhibitory binding proteins, is involved in multiple physiological processes associated with cardiovascular disease. This review will describe the various roles of PAPP-A with a focus on atherosclerosis, neointimal hyperplasia, and acute coronary syndrome in animal models and in humans.

有确凿证据表明，PAPP-A 是胰岛素样生长因子信号传导的局部调节因子，它通过蛋白水解作用裂解抑制性结合蛋白，参与多种与心血管疾病相关的生理过程。本综述将介绍 PAPP-A 的各种作用，重点是动物模型和人体中的动脉粥样硬化、新内膜增生和急性冠状动脉综合征。

引用次数: 0

Medical treatment of acromegaly – When the tumor size matters: A narrative review 肢端肥大症的药物治疗--当肿瘤大小很重要时：叙述性综述。

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2024-08-02 DOI: 10.1016/j.ghir.2024.101608

Mirjana Doknic , Marko Stojanovic , Dragana Miljic , Mihajlo Milicevic

Medical treatment of acromegaly is generally positioned as a second line of treatment after pituitary adenoma surgery. With the rising availability and variety of medications for acromegaly increases our understanding of their effectiveness and safety. Volume of the published data on the impact of medical therapy on biochemical control of acromegaly, contrasts a relative lack of publications which comprehensively address pituitary tumor alterations under different drug modalities. Assessment of changes in GH-secreting adenoma volume is often overshadowed by clinicians' focus on GH and IGF-I levels during acromegaly treatment. Close analysis of studies published in the last two decades, reveals that both an increase and decrease in somatotropinoma volume are possible during treatment with any of available drugs for acromegaly. Changes in pituitary tumor size may arise from the biological nature of adenoma itself, independently of the administered medications. Therefore, an individual approach is necessary in the treatment of patients with acromegaly, based on repeated insight to their clinical, biochemical, pathological and imaging characteristics. In this review, we summarize and comment how pituitary tumor size is affected by the treatment with all currently available drugs in acromegaly: long-acting somatostatin receptor ligands of the first generation (octreotide LAR and lanreotide autogel) and the second generation (pasireotide-LAR), as well as pegvisomant (PEG) and cabergoline (CAB).

肢端肥大症的药物治疗一般被定位为垂体腺瘤手术后的第二线治疗。随着治疗肢端肥大症的药物越来越多，种类也越来越丰富，我们对这些药物的有效性和安全性也有了更多的了解。已发表的关于药物治疗对肢端肥大症生化控制的影响的大量数据与全面探讨不同药物治疗模式下垂体瘤变化的出版物相对缺乏形成鲜明对比。在肢端肥大症治疗过程中，临床医生对 GH 和 IGF-I 水平的关注往往掩盖了对分泌 GH 腺瘤体积变化的评估。对过去二十年发表的研究进行仔细分析后发现，在使用任何现有药物治疗肢端肥大症的过程中，体细胞瘤体积都有可能增大或缩小。垂体瘤体积的变化可能源于腺瘤本身的生物学特性，与用药无关。因此，在对肢端肥大症患者进行治疗时，有必要在反复了解其临床、生化、病理和影像学特征的基础上，采取因人而异的方法。在这篇综述中，我们总结并评论了垂体瘤的大小如何受到目前所有治疗肢端肥大症药物的影响：第一代长效体泌素受体配体（奥曲肽 LAR 和 Lanreotide autogel）、第二代长效体泌素受体配体（帕司瑞奥肽 LAR）、培维索曼（PEG）和卡麦角林（CAB）。

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引用次数: 0

Adult patients with Laron syndrome tend to develop the metabolic syndrome 患有拉隆综合征的成年患者往往会发展成代谢综合征

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2024-07-25 DOI: 10.1016/j.ghir.2024.101605

Zvi Laron, Rivka Kauli, Avivah Silbergeld

Background

The metabolic Syndrome is the name of a cluster of abnormal clinical and metabolic states, which constitute a risk factor for diabetes and cardiovascular disease.

Aim

To determine whether adult patients with Laron Syndrome with excessive obesity develop the characteristics of the Metabolic Syndrome.

Subjects

Out of a cohort of adult patients with Laron Syndrome followed in our clinic, records of 23 patients (12 females, 11 males) were found to have sufficient data for analysis.

Methods

The degree of obesity was determined by the measurement of subscapular skinfold thickness (SSFT), BMI and total body DEXA. NAFLD was determined by liver ultrasonography, serum lipids including adiponectin leptin, insulin and glucose were assessed by radioimmunoassay.

Results

Both female and male patients were markedly obese with 59% and 39% fat of the total body mass respectively, as were total and LDL cholesterol, triglycerides and adiponectin. Some had developed NAFLD. They also suffered from insulin resistance and glucose intolerance. Eleven patients (3 females, 8 males) developed diabetes. All had varying degrees of hypertension. Eight subjects (3 females, 5 males) suffered from cardiovascular disease. One female died at aged 53 years, and two males died at ages 75 and 78 years.

Conclusion

With advancing age and increasing obesity, adult patients with Laron Syndrome developed the characteristics of Metabolic Syndrome including diabetes and cardiovascular disease.

背景代谢综合征是一组异常临床和代谢状态的名称，是糖尿病和心血管疾病的危险因素。方法通过测量肩胛下皮褶厚度（SSFT）、体重指数（BMI）和全身 DEXA 来确定肥胖程度。通过肝脏超声波检查确定非酒精性脂肪肝，通过放射免疫测定法评估血清脂质（包括脂肪连蛋白瘦素）、胰岛素和葡萄糖。有些人还出现了非酒精性脂肪肝。他们还患有胰岛素抵抗和葡萄糖不耐受症。11 名患者（3 名女性，8 名男性）患上了糖尿病。所有患者都患有不同程度的高血压。八名受试者（3 名女性，5 名男性）患有心血管疾病。结论随着年龄的增长和肥胖的加剧，拉隆综合征成年患者出现了代谢综合征的特征，包括糖尿病和心血管疾病。

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引用次数: 0