Growth Hormone & Igf Research最新文献_第2页

Dose optimization of PEG-rhGH therapy to improve growth outcomes of childhood-onset growth failure PEG-rhGH治疗的剂量优化以改善儿童期起病生长衰竭的生长结局。

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2025-10-01 Epub Date: 2025-09-12 DOI: 10.1016/j.ghir.2025.101664

Ying Wu , Lai Zhang , Haipeng Ma, Peng Wang, Ming Lu, Xinle Xv, Sheng Yu

Background

This study evaluates the efficacy and safety of optimized PEG-rhGH dosing in pre-pubertal and pubertal children with Childhood-Onset Growth Failure due to growth hormone deficiency (GHD) or non-GHD causes.

Methods

This study employed a combined retrospective (n = 144) and prospective (n = 14) design to examine the PEG-rhGH dosing strategies' impact. A total of 158 children were enrolled in the study, of whom 130 were included in the analysis after completing a minimum of one year of follow-up. Participants were stratified into pre-pubertal and pubertal groups. PEG-rhGH therapy with dose titration was administered based on growth response and IGF-1 level. The primary goal of the study was to evaluate the effect of individualized PEG-rhGH dosing, including clinically-based target height velocity and IGF-1 titration, on height velocity in children with GHD and non-GHD small children, stratified by puberty. Outcome measures included change in height, weight, BMI, and adverse events. Data were analyzed with SPSS 25.0.

Results

Pre-pubertal children exhibited a significantly greater height increase compared to pubertal adolescents (9.75 cm vs. 9.01 cm, p = 0.0159). A dose-dependent effect on growth velocity was observed in both groups. In the pubertal group, growth velocity (GV) increased from 0.80 ± 0.20 cm/year at doses ≤0.200 mg/kg/week to 0.99 ± 0.38 cm/year at doses ≥0.220 mg/kg/week (p = 0.017). Similarly, in the pre-pubertal group, GV increased from 0.87 ± 0.23 cm/year at the lowest dose to 1.10 ± 0.24 cm/year at the highest dose (p = 0.048). These findings confirm a dose-response relationship, particularly at doses exceeding 0.200 mg/kg/week.

Conclusions

PEG-rhGH therapy was more effective in promoting height growth in pre-pubertal children compared to pubertal adolescents. A clear dose-dependent effect was observed in both groups, emphasizing the importance of individualized dosing for optimal growth outcomes.

背景：本研究评估了优化PEG-rhGH剂量对由生长激素缺乏症（GHD）或非GHD原因导致的儿童性生长衰竭的青春期前和青春期儿童的疗效和安全性。方法：本研究采用回顾性（n = 144）和前瞻性（n = 14）相结合的设计来检查PEG-rhGH给药策略的影响。共有158名儿童参加了这项研究，其中130名在完成至少一年的随访后被纳入分析。参与者被分为青春期前组和青春期组。根据生长反应和IGF-1水平进行PEG-rhGH剂量滴定治疗。该研究的主要目的是评估个体化PEG-rhGH剂量的影响，包括基于临床的目标身高速度和IGF-1滴定，对GHD儿童和非GHD儿童的身高速度，按青春期分层。结果测量包括身高、体重、BMI和不良事件的变化。数据采用SPSS 25.0进行分析。结果：青春期前儿童身高增长明显高于青春期后儿童（9.75 cm比9.01 cm, p = 0.0159）。在两组中均观察到对生长速度的剂量依赖效应。发育期组的生长速率（GV）由≤0.200 mg/kg/周时的0.80±0.20 cm/年增加到≥0.220 mg/kg/周时的0.99±0.38 cm/年（p = 0.017）。同样，在青春期前组，GV从最低剂量的0.87±0.23 cm/年增加到最高剂量的1.10±0.24 cm/年（p = 0.048）。这些发现证实了剂量-反应关系，特别是在剂量超过0.200 mg/kg/周时。结论：PEG-rhGH治疗在促进青春期前儿童身高增长方面比青春期青少年更有效。在两组中都观察到明显的剂量依赖效应，强调了个体化给药对最佳生长结果的重要性。

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引用次数: 0

The effect of treatment with somatostatin analogs in children with neurofibromatosis type 1 and growth hormone excess 生长抑素类似物治疗1型神经纤维瘤病和生长激素过量的效果

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2025-10-01 Epub Date: 2025-10-21 DOI: 10.1016/j.ghir.2025.101667

Sofie Skov Koch , Jonathan Frederik Carlsen , Cecilie Ejerskov , Ulla Feldt-Rasmussen , Katharina M. Main , Astrid Sehested , Rene Mathiasen , Sarah Linea von Holstein , Stense Farholt , Rikke Beck Jensen

Context

Growth hormone (GH) excess in children is rare but may be seen in children with neurofibromatosis type 1 (NF1) and is then often associated with optic pathway glioma (OPG).

Objective

The aim of this study was to determine anthropometrics and the efficacy of treatment in patients with NF1 and GH excess. Additionally, to examine the association between GH excess and OPG.

Design

A descriptive, retrospective study on nine patients with NF1 and GH excess referred to a tertiary center of pediatric endocrinology.

Setting: Single tertiary center.

Patients

Nine patients with GH excess and NF1 were routinely followed by pediatric endocrinologists for clinical evaluation, anthropometrics, and hormone analysis. All patients underwent brain Magnetic Resonance Imaging (MRI) and all the scans were reevaluated for classification of the OPGs. Furthermore, the patients were routinely followed by ophthalmologists.

Main outcome measures

Anthropometrics and IGF-I levels expressed as standard deviation scores (SDS).

Results

The patients presented with height velocity (HV) (SDS), height (SDS) and IGF-I (SDS) above the normal reference range. Eight out of nine patients had OPGs, seven of which with hypothalamic involvement. They were treated with somatostatin analogs (SSas). Within the first year of treatment, IGF-I (SDS) levels decreased rapidly and normalized in all patients within two to three and a half years.

Conclusion

Rapid growth in children with NF1 requires further evaluation especially in those with OPG since it could be a caused by GH excess. Treatment of GH excess with SSas was effective.

儿童生长激素（GH）过量是罕见的，但可能在1型神经纤维瘤病（NF1）儿童中看到，然后通常与视神经胶质瘤（OPG）相关。目的本研究的目的是确定NF1和GH过量患者的人体测量学和治疗效果。此外，研究生长激素过量和OPG之间的关系。设计：对9例NF1和GH过量患者进行描述性、回顾性研究，这些患者被转介到儿科内分泌学三级中心。设置：单三级中心。儿童内分泌学家对9例生长激素过量和NF1患者进行常规随访，进行临床评估、人体测量学和激素分析。所有患者均接受脑磁共振成像（MRI）检查，并重新评估所有扫描结果以确定OPGs的分类。此外，眼科医生对患者进行了常规随访。主要结果测量：人体测量和IGF-I水平以标准差评分（SDS）表示。结果患者身高速度（HV）、身高（SDS）、IGF-I （SDS）均高于正常参考范围。9名患者中有8名患有opg，其中7名与下丘脑有关。给予生长抑素类似物（SSas）治疗。在治疗的第一年，所有患者的IGF-I （SDS）水平迅速下降，并在2至3年半内恢复正常。结论NF1患儿的快速生长需要进一步评估，特别是OPG患儿，因为它可能是由生长激素过量引起的。用SSas治疗生长激素过量是有效的。

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引用次数: 0

Growth hormone regulates deiodinase type 2 and 3 expression via GATA 生长激素通过GATA调控2型和3型脱碘酶的表达

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2025-10-01 Epub Date: 2025-05-21 DOI: 10.1016/j.ghir.2025.101659

Mana Mitsutani , Hiromi Hano , Mei Yokoyama , Midori Matsushita , Misa Hayashi , Ichiro Yamauchi , Tetsuya Tagami , Kenji Moriyama

Objective

Growth hormone (GH) is involved in bone and skeletal muscle growth directly or indirectly via STAT5 and/or insulin-like growth factor (IGF)-1. Thyroid hormone (TH) is essential for general cellular growth and metabolic regulation. While both GH and TH are essential for growth, their actions may partially complement each other in conditions of hormonal deficiency. For example, TH can enhance GH secretion and sensitivity, while GH is ineffective in Refetoff syndrome due to TH receptor dysfunction. However, the underlying molecular mechanism remains unclear. In this study, we investigated the molecular mechanisms underlying the complementarity between GH and TH, paying special attention to the effects of GH on the expression of both iodothyronine deiodinase (DIO) type 2 (DIO2) and type 3 (DIO3).

Design

The effects of growth hormone (GH) on DIOs were examined using reporter assays, chromatin immunoprecipitation, quantitative PCR, and western blotting using HEK293-derived TSA201 cells and mouse ATDC5 chondrocytes.

Results

GH induced the mRNA and protein expression of DIOs in ATDC5 cells via STAT5/GATA. GATAs activate the promoter activity of both DIOs. The binding sites for GATA on the DIO promoter were located −87 bp and − 75 bp upstream from the TSS for the DIO2 promoter and − 6 bp upstream from the TSS for the DIO3 promoter, respectively. GH-induced expression of DIOs in ATDC5 cells was abolished by K-7174, a GATA-specific inhibitor.

Conclusion

The present study demonstrates that GH regulates DIO2 and DIO3 expression via JAK/STAT5/GATAs after binding to GHR. This is the first report on the molecular mechanisms underlying GH-dependent compensation of TH action. (256 words).

目的：生长激素（GH）通过STAT5和/或胰岛素样生长因子(IGF)-1直接或间接参与骨和骨骼肌生长。甲状腺激素（TH）是一般细胞生长和代谢调节所必需的。虽然生长激素和促甲状腺激素都是生长所必需的，但在激素缺乏的情况下，它们的作用可能部分互补。例如，TH可以增强GH的分泌和敏感性，而GH由于TH受体功能障碍，对Refetoff综合征无效。然而，潜在的分子机制尚不清楚。在这项研究中，我们研究了GH和TH互补的分子机制，特别关注GH对碘甲状腺原氨酸脱碘酶（DIO） 2型（DIO2）和3型（DIO3）表达的影响。使用hek293衍生的TSA201细胞和小鼠ATDC5软骨细胞，采用报告基因法、染色质免疫沉淀法、定量PCR和western blotting检测生长激素（GH）对DIOs的影响。结果gh通过STAT5/GATA诱导ATDC5细胞中DIOs mRNA和蛋白的表达。GATAs激活两个DIOs的启动子活性。GATA在DIO启动子上的结合位点分别位于DIO2启动子的TSS上游- 87 bp和- 75 bp， DIO2启动子的TSS上游- 6 bp。gata特异性抑制剂K-7174可抑制gh诱导的ATDC5细胞中DIOs的表达。结论GH与GHR结合后，通过JAK/STAT5/GATAs调控DIO2和DIO3的表达。这是关于gh依赖的TH作用补偿的分子机制的第一份报告。(256字)。

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引用次数: 0

Efficacy, safety, and outcomes of growth hormone treatment in children with idiopathic short stature 生长激素治疗特发性矮小儿童的疗效、安全性和结局

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2025-10-01 Epub Date: 2025-08-09 DOI: 10.1016/j.ghir.2025.101661

Agnès Linglart , Andrew Dauber , Alexander de Lima Jorge , Xiaoping Luo , Tsutomu Ogata , Lars Sävendahl

Background

Growth hormone (GH) is a treatment option in some countries for children with idiopathic short stature (ISS) given to enable them to attain height within the expected range. Currently, it is not often utilised in clinical practice. A literature review was conducted to summarise the efficacy, safety, and outcomes associated with GH treatment in children with ISS.

Summary

Guidelines for the diagnosis and treatment of ISS may benefit from revision to accommodate recent findings on genetic factors that influence height. Clinical trials and observational studies designed to investigate the effect of GH treatment on children with ISS have shown that it is effective in enabling them to attain height within the normal range. In some instances, height improvements are reported up to adult height. The safety of GH treatment in this patient population has also been investigated and no new safety concerns have been observed. In analyses that were designed to investigate the effect of GH on quality of life, improvements in psychosocial scores were observed, either by the patient, parent, or the treating physician.

Key message

GH treatment is effective in improving height outcomes and quality of life in children with ISS, with an acceptable safety profile.

在一些国家，生长激素（GH）是特发性身材矮小（ISS）儿童的一种治疗选择，用于使他们达到预期范围内的身高。目前，它在临床实践中并不常用。一篇文献综述总结了生长激素治疗ISS患儿的有效性、安全性和相关结果。摘要：ISS的诊断和治疗指南可能会受益于修订，以适应影响身高的遗传因素的最新发现。旨在调查生长激素治疗对ISS儿童影响的临床试验和观察性研究表明，它能有效地使他们达到正常范围内的身高。在某些情况下，身高的提高可以达到成人的身高。生长激素治疗在这一患者群体中的安全性也进行了调查，没有观察到新的安全问题。在旨在调查生长激素对生活质量影响的分析中，无论是患者、父母还是治疗医生都观察到心理社会评分的改善。关键信息：egh治疗可有效改善ISS患儿的身高结局和生活质量，并具有可接受的安全性。

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引用次数: 0

Effects of insulin-like growth factor-I and Progranulin on a human trophoblast model 胰岛素样生长因子- 1和蛋白原对人滋养细胞模型的影响。

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2025-10-01 Epub Date: 2025-09-22 DOI: 10.1016/j.ghir.2025.101665

Makoto Osaka, Atsushi Tajima, Satoshi Takemori, Momoe Watanabe, Tohru Morisada, Shinji Tanigaki, Yoichi Kobayashi

Gestational diabetes and obesity are associated with increased placental weight and fetal birth weight. Placental development is mainly promoted by trophoblast proliferation and various humoral factors. Insulin-like growth factor-1 (IGFI) levels are increased in mothers with gestational diabetes, and trophoblast proliferation is promoted in a dose-dependent manner. In addition, progranulin (PGRN), an adipokine involved in obesity, plays an important role in the proliferation of trophoblast cell lines. IGF-I and PGRN independently affect placental development, but there are many unknowns regarding their interaction. In this study, we investigated the combined effects of IGF-I and PGRN on trophoblast proliferation using the human choriocarcinoma cell line JEG-3. Cell proliferation was evaluated using a cell counting method and a water-soluble tetrazolium-1 assay. Furthermore, the effect of PGRN on the intracellular signaling pathways of IGFI, particularly the phosphorylation of Akt and Erk1/2, was evaluated using western blotting. IGF-I significantly increased cell proliferation in JEG-3 cells. However, the proliferative effect of a low concentration of IGF-I (100 ng/mL) was inhibited by simultaneous treatment with PGRN. Pretreatment with PGRN significantly suppressed phosphorylation of Erk1 at a low concentration of IGF-I (P < 0.01) but had no effect on phosphorylation of Akt. PGRN may suppress IGF-I-induced trophoblast proliferation by regulating the phosphorylation of Erk1/2, especially at low concentrations of IGFI. PGRN modulates the proliferative effects of IGF-I in a complex manner, dependent on the concentration and timing of exposure. These findings indicate that the placental growth factor IGF-I may be regulated by PGRN.

(245 words)

妊娠期糖尿病和肥胖症与胎盘体重和胎儿出生体重增加有关。胎盘发育主要受滋养细胞增殖和各种体液因子的促进。妊娠期糖尿病母亲的胰岛素样生长因子-1 （IGFI）水平升高，滋养细胞增殖呈剂量依赖性。此外，前颗粒蛋白（PGRN）是一种与肥胖有关的脂肪因子，在滋养细胞系的增殖中起重要作用。IGF-I和PGRN分别影响胎盘发育，但它们之间的相互作用仍有许多未知因素。本研究以人绒毛膜癌细胞系JEG-3为实验对象，研究了igf - 1和PGRN对滋养细胞增殖的联合作用。用细胞计数法和水溶性四氮唑-1测定法评价细胞增殖。此外，PGRN对IGFI细胞内信号通路的影响，特别是Akt和Erk1/2的磷酸化，采用western blotting进行了评估。igf - 1显著促进了JEG-3细胞的增殖。然而，低浓度IGF-I （100 ng/mL）的增殖作用被PGRN同时抑制。PGRN预处理显著抑制低浓度IGF-I的Erk1磷酸化(P

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引用次数: 0

Dynamic changes in IGF-1 levels during cabergoline therapy in prolactinoma 卡麦角林治疗催乳素瘤期间IGF-1水平的动态变化。

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2025-10-01 Epub Date: 2025-10-14 DOI: 10.1016/j.ghir.2025.101669

Ahmet Numan Demir , Alara Birol , Dilan Ozaydin , Zehra Kara , Serdar Sahin , Pinar Kadioglu

Background

Cabergoline, a dopamine agonist widely used in prolactinoma treatment, also suppresses growth hormone (GH) and insulin-like growth factor-1 (IGF-1), though its long-term effects on IGF-1 levels in prolactinoma remain unclear.

Objective

To evaluate changes in IGF-1 levels and influencing factors in prolactinoma patients treated with cabergoline.

Methods

This retrospective cohort study included 127 prolactinoma patients treated with cabergoline between 2013 and 2023. Patients with conditions affecting IGF-1 (e.g., hypopituitarism, organ dysfunction, hormone replacement therapy) were excluded. IGF-1 and IGF-1xULN levels were compared at baseline and last follow-up. Associations with treatment duration, cumulative cabergoline dose, and tumor features were assessed using regression and ROC analyses.

Results

The median follow-up was 36 [IQR: 18–60] months. Final IGF-1 and IGF-1xULN levels were significantly lower than baseline (p = 0.002 and p = 0.045). IGF-1xULN increased in 44.9 % and decreased in 55.1 % of patients, but all values remained within normal limits. Decreased IGF-1xULN was associated with longer treatment duration and higher cumulative doses (p < 0.05). ROC analysis identified ≥60 mg cumulative dose and ≥ 18 months treatment duration as predictors of IGF-1 reduction (AUROC ≈ 0.70).

Conclusion

Cabergoline therapy in prolactinoma may result in an early rise and subsequent decline in IGF-1 levels. The clinical significance of within-range IGF-1 reductions remains uncertain and requires prospective studies with predefined metabolic endpoints.

背景：卡麦角林是一种广泛用于催乳素瘤治疗的多巴胺激动剂，它也能抑制生长激素（GH）和胰岛素样生长因子-1 (IGF-1)，但其对催乳素瘤中IGF-1水平的长期影响尚不清楚。目的：探讨卡麦角林治疗催乳素瘤患者IGF-1水平的变化及其影响因素。方法：本回顾性队列研究纳入2013年至2023年间接受卡麦角林治疗的127例催乳素瘤患者。排除影响IGF-1的患者（如垂体功能减退、器官功能障碍、激素替代治疗）。在基线和最后一次随访时比较IGF-1和IGF-1xULN水平。使用回归和ROC分析评估与治疗时间、卡麦角林累积剂量和肿瘤特征的关系。结果：中位随访36个月[IQR: 18-60]个月。最终IGF-1和IGF-1xULN水平显著低于基线（p = 0.002和p = 0.045）。IGF-1xULN在44.9%的患者中升高，55.1%的患者中降低，但所有值都保持在正常范围内。降低的IGF-1xULN与较长的治疗时间和较高的累积剂量相关(p结论：卡麦角林治疗催乳素瘤可能导致IGF-1水平的早期升高和随后的下降。IGF-1在范围内降低的临床意义仍然不确定，需要预先设定代谢终点的前瞻性研究。

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引用次数: 0

Injection of lentiviral vectors expressing GH and IGF1 increases body and muscle mass in male rats 注射表达生长激素和IGF1的慢病毒载体可增加雄性大鼠的体重和肌肉质量

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2025-10-01 Epub Date: 2025-08-28 DOI: 10.1016/j.ghir.2025.101663

Zahra Roudbari , Akram Alizadeh , Mohammadreza Nassiri , Ali Fallah , Ali Javadmanesh

The aim of this study was to increase growth hormone (GH1) and insulin-like growth factor-1 (IGF1) levels in rat muscle indirectly through the transduction of C2C12 cells via lentivectors and to compare their effects on muscle mass. The coding sequences of GH1, IGF1, and GH1-IGF1, linked by the 2 A self-cleaving peptide to enable polycistronic expression, were synthesized, cloned and inserted into the pCDH vector. Recombinant pseudolentiviruses containing our target genes were produced in HEK293T cells. C2C12 cells were transduced with pseudo lentiviruses and selected through resistance to puromycin antibiotics. The expression of the GH1 and IGF1 genes at the mRNA and protein levels was verified by RT–PCR and Western blotting, respectively. The recombinant pseudo lentiviruses and transduced C2C12 cells were injected into the tibialis anterior (TA), gastrocnemius and quadriceps muscle groups of eight-week-old rats. The body weights of the rats were measured weekly for eight weeks after the injection. The leg weight and histology of the muscle after eight weeks were also measured. The results revealed the expression of the GH1 and IGF1 genes at the mRNA and protein levels in C2C12 cells. An increase in both hormones, either directly or indirectly through C2C12 cells, increased the animal body weight, leg weight, and muscle fibre size after eight weeks. The direct and indirect transfer of IGF1 increased body weight, leg weight and muscle fibre size more than did the direct or indirect transfer of GH1. In the direct transfer groups, the body weight was greater than that in the indirect transfer groups after eight weeks. We demonstrated that nonpituitary secretion of GH1 mimicked some physiological effects of pituitary GH1 in a rat model. Further investigations are needed to study other possible effects of extra copy of GH1 and IGF1 genes over a longer period on other tissues.

本研究的目的是通过慢载体介导C2C12细胞间接增加大鼠肌肉中生长激素（GH1）和胰岛素样生长因子-1 （IGF1）的水平，并比较它们对肌肉质量的影响。合成GH1、IGF1和GH1-IGF1编码序列，通过2a自裂肽连接，实现多顺反子表达，克隆并插入pCDH载体。在HEK293T细胞中产生了含有我们的靶基因的重组假病毒。用伪慢病毒转导C2C12细胞，通过对嘌呤霉素耐药筛选。RT-PCR和Western blotting分别检测GH1和IGF1基因在mRNA和蛋白水平上的表达。将重组伪慢病毒和转导的C2C12细胞注射于8周龄大鼠胫骨前肌、腓肠肌和股四头肌群。注射后8周，每周测量大鼠体重。8周后还测量了腿部重量和肌肉组织学。结果显示，GH1和IGF1基因在C2C12细胞中mRNA和蛋白水平表达。8周后，直接或间接通过C2C12细胞增加的两种激素增加了动物的体重、腿重和肌肉纤维大小。IGF1的直接和间接传递比GH1的直接和间接传递更能增加体重、腿重和肌纤维大小。8周后，直接转移组的体重明显大于间接转移组。我们在大鼠模型中证明了GH1的非垂体分泌模拟了垂体GH1的一些生理作用。需要进一步研究GH1和IGF1基因的额外拷贝在较长时间内对其他组织的其他可能影响。

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引用次数: 0

Exploring GHBP as a surrogate of GH activity in multimorbid older adults: A cross-sectional study 探索GHBP作为多种疾病老年人生长激素活性的替代品：一项横断面研究

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2025-10-01 Epub Date: 2025-09-29 DOI: 10.1016/j.ghir.2025.101666

Olivia Tausendfreund , Martin Bidlingmaier , Michael Haenelt , Tim Kuehnle , Linda Deissler , Sebastian Martini , Katharina Mueller , Michaela Rippl , Katharina Schilbach , Sabine Schluessel , Ralf Schmidmaier , Michael Drey

Introduction

With the rise of aging societies and complex multimorbidity, age related endocrine alterations such as insulin-like growth factor I (IGFI) deficiency gain clinical importance. Beyond reduced growth hormone (GH) secretion, GH resistance represents an additional mechanism contributing to IGF-I deficiency, potentially aggravating age-related diseases.

Purpose

This study investigates whether multimorbid, high-aged patients with IGF-I deficiency exhibit a form of acquired peripheral GH resistance, as indicated by altered GH-binding protein (GHBP) concentrations.

Materials and methods

In a cross-sectional design we conducted a retrospective analysis of serum samples of 759 patients from the geriatric day clinic and acute geriatric ward of the Ludwig-Maximilians-University Hospital, Munich.

Results

The mean age was 81 years, with a mean baseline IGF-I of 85 ng/ml (corresponding to −0.07/−0.1 SDS in males/females), a mean GHBP concentration of 751 pM and a mean GH concentration of 1.68 ng/ml. Patients with IGF-I concentrations below 2 standard deviation score (SDS) exhibited significantly elevated GH alongside reduced GHBP, suggestive of a peripheral GH resistance (n = 48). In contrast, the subgroup (n = 26) with the highest IGF-I concentrations (up to 2 SDS), demonstrated elevated GH and high GHBP concentrations.

Conclusion

Our findings suggest that low GHBP may indicate acquired peripheral GH resistance in a subset of multimorbid, high-aged patients. Further functional endocrine testing, including IGF-I generation test is necessary. Analysis of the subgroup with above-average IGF-I concentrations could provide insights into longevity and on the safety of GH and IGF-I treatment.

随着老龄化社会的兴起和复杂的多病，年龄相关的内分泌改变，如胰岛素样生长因子I （IGFI）缺乏，在临床中具有重要意义。除了生长激素（GH）分泌减少外，GH耐药性是导致IGF-I缺乏的另一种机制，可能会加重与年龄相关的疾病。目的：本研究探讨多种疾病的高龄IGF-I缺乏症患者是否表现出一种获得性外周生长激素抵抗，如GH结合蛋白（GHBP）浓度改变所表明的那样。材料和方法采用横断面设计，对慕尼黑路德维希-马克西米利安大学医院老年日间门诊和急性老年病房759例患者的血清样本进行回顾性分析。结果平均年龄81岁，平均基线IGF-I为85 ng/ml（男性/女性为- 0.07/ - 0.1 SDS），平均GHBP浓度为751 pM，平均GH浓度为1.68 ng/ml。IGF-I浓度低于2个标准差评分（SDS）的患者表现出显著的生长激素升高和GHBP降低，提示外周生长激素抵抗（n = 48）。相反，IGF-I浓度最高的亚组（n = 26）（高达2 SDS）显示GH和GHBP浓度升高。结论：我们的研究结果表明，低GHBP可能表明在多病的高龄患者中存在获得性外周生长激素抵抗。进一步的内分泌功能测试，包括IGF-I生成测试是必要的。对IGF-I浓度高于平均水平的亚组进行分析，可以深入了解生长激素和IGF-I治疗的寿命和安全性。

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引用次数: 0

Corrigendum to “Pharmacodynamics, pharmacokinetics, and toxicology of Fc-growth hormone fusion protein in macaques” 《猕猴体内fc -生长激素融合蛋白的药效学、药代动力学和毒理学》的勘误表

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2025-06-01 Epub 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 fc -生长激素融合蛋白在猕猴体内的药效学、药代动力学和毒理学研究

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2025-06-01 Epub 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.

目的：生长激素（GH）治疗生长激素缺乏症可用于治疗多种疾病。然而，生长激素的半衰期短，需要频繁给药，这限制了患者的依从性。Fc融合蛋白是通过将活性肽与IgG的Fc部分结合而产生的，已知可以延长肽的血浆半衰期。Fc-GH在大鼠体内的药效学和药代动力学已有报道；然而，缺乏对灵长类动物模型的研究。因此，在本研究中，我们旨在研究Fc-GH在恒河猴和食蟹猕猴体内的药效学、药代动力学和毒理学。方法恒河猴分别以0.8、1.6、3.2 mg/kg皮下注射和1.6 mg/kg静脉注射Fc-GH。1.6 mg/kg皮下给药5次，每7天1次；其他剂量以单次注射方式进行药效学和药代动力学评估。对食蟹猕猴进行30、45和62.5 mg/kg单次皮下注射，并每7天重复注射一次3、10和30 mg/kg，随后8周恢复，评估潜在毒性。结果给药后无不良反应发生。Fc-GH在皮下给药后缓慢达到Cmax，在静脉给药后迅速达到Cmax，血浆水平随时间保持不变。恒河猴的半衰期分别为23.72±2.17 h （0.8 mg/kg）、49.44±14.77 h （1.6 mg/kg）和76.07±13.19 h （3.2 mg/kg）。注射5次1.6 mg/kg后，Fc-GH的半衰期为60.42±18.29 h，胰岛素样生长因子1 （IGF-1）和胰岛素样生长因子结合蛋白3 （IGFBP-3）水平显著升高，并在注射后28-42 d内保持升高。在食蟹猕猴中，未观察到Fc-GH积累。单次皮下最大耐受剂量为62.5 mg/kg；在30 mg/kg的剂量下重复给药29次，恢复时间为8周，未观察到不良反应。结论sfc - gh在猕猴体内具有良好的药代动力学和药效学特性，可显著延长半衰期，提高IGF-1和IGFBP-3水平，且无不良反应。这些发现表明Fc-GH是一种很有希望的长效生长激素疗法，可以提高患者的依从性。

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