Growth Hormone & Igf Research最新文献

Auxology – an update 2025 Auxology - 2025年更新

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2026-01-14 DOI: 10.1016/j.ghir.2026.101680

María Belén Tite Haro , Christiane Scheffler , Michael Hermanussen

Growth is a dynamic process and a mirror of health. Documenting child and adolescent growth includes careful, and if possible, longitudinal recordings of height, weight, and indicators of the state of maturity. Measurements should be translated into centiles or z-scores. Changes in height z-scores are related to the progress in maturation, and sensitive to growth arrests and catch-up growth.

Heritability studies and genome-wide association studies have traditionally been applied to assess the intrinsic regulators of growth. Nutritional, environmental and socio-economic factors are usually considered the major extrinsic regulators of growth.

Human growth is not a target seeking process, but a process that unfolds within a frame shaped and regulated primarily by the social community of family, peers, and neighbors. Community effects on height protect against being “too tall” or “too short” within a given social group.

In the healthy individual, height is a social signal which is strongly conserved in evolution. Height refers to social status among members of the same group, and is strategically regulated through neuroendocrine signals. Strategic adjustments of growth are part of social interactions. Being taller signals supremacy and dominance, being shorter signals inferiority.

Global growth charts are insufficient to reflect the social and historic plasticity of human growth, and can lead to misclassification of “normal” and “abnormal” growth within a given population.

成长是一个动态的过程，是健康的一面镜子。记录儿童和青少年的成长包括仔细的，如果可能的话，纵向记录身高、体重和成熟状态的指标。测量值应该转换成百分位或z分数。身高z分数的变化与成熟进程有关，对生长停滞和追赶生长敏感。遗传力研究和全基因组关联研究传统上被用于评估生长的内在调节因子。营养、环境和社会经济因素通常被认为是生长的主要外在调节因素。人的成长不是一个追求目标的过程，而是在一个主要由家庭、同伴和邻居等社会团体塑造和调节的框架内展开的过程。在一个特定的社会群体中，社区对身高的影响可以防止“太高”或“太矮”。在健康个体中，身高是一种社会信号，在进化过程中是高度保守的。身高是指在同一群体成员中的社会地位，并通过神经内分泌信号进行战略性调节。增长的战略性调整是社会互动的一部分。个子高表示至高无上和支配地位，个子矮表示自卑。全球增长图表不足以反映人类增长的社会和历史可塑性，并可能导致对特定人口中“正常”和“异常”增长的错误分类。

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引用次数: 0

The growth plate: Zonal architecture, plasticity, and endocrine control of linear growth 生长板：带状结构，可塑性，和内分泌控制线性生长。

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2026-01-07 DOI: 10.1016/j.ghir.2026.101679

Carlos Barba Ostria , Shoshana Yakar

The growth plate (physis) is a highly specialized cartilaginous organ that drives longitudinal bone growth and ultimately determines adult stature. Its zonal architecture, including the resting, proliferative, hypertrophic, and calcification zones, integrates stem-like progenitor activity, clonal chondrocyte expansion, matrix remodeling, vascular invasion, and replacement by bone. Here, we review how the structural organization of the growth plate emerges from the interplay among extracellular matrix composition, sulfation pathways, and canonical paracrine signaling pathways, including Ihh-PTHrP, BMP, Wnt, and FGF. We highlight advances in our understanding of chondrocyte fate, including lineage-tracing studies demonstrating that resting-zone PTHrP⁺ cells function as skeletal stem cells and that hypertrophic chondrocytes can transdifferentiate into osteoblasts or dedifferentiate into progenitors rather than undergoing obligatory apoptosis. We also summarize how endocrine axes, including the GH/IGF-1, thyroid hormone, sex steroids, glucocorticoids, and vitamin D, coordinate the tempo of growth, the dynamics of growth plate senescence, and the timing of epiphyseal fusion, with emphasis on species differences between rodents and humans. Finally, we use monogenic skeletal dysplasias, endocrine disorders, and acquired conditions such as rickets and slipped capital femoral epiphysis as “experiments of nature” that illuminate how specific molecular perturbations disrupt growth plate physiology. Together, these converging lines of evidence reframe the growth plate as a dynamic stem-cell and progenitor niche whose fate is plastic, highly regulated, and increasingly targetable for therapy in disorders of linear growth.

生长板（骨骺）是一种高度特化的软骨器官，它驱动纵向骨生长并最终决定成人的身高。其分带结构包括静息区、增生区、肥厚区和钙化区，整合了干细胞样祖细胞活性、克隆软骨细胞扩张、基质重塑、血管侵入和骨替代。在这里，我们回顾了生长板的结构组织是如何从细胞外基质组成、硫酸化途径和典型旁分泌信号通路（包括Ihh-PTHrP、BMP、Wnt和FGF）之间的相互作用中产生的。我们强调了我们对软骨细胞命运的理解的进展，包括谱系追踪研究表明静息区PTHrP+细胞具有骨骼干细胞的功能，肥厚软骨细胞可以转分化为成骨细胞或去分化为祖细胞，而不是经历强制性凋亡。我们还总结了内分泌轴，包括GH/IGF-1、甲状腺激素、性类固醇、糖皮质激素和维生素D，如何协调生长速度、生长板衰老的动态和骨骺融合的时间，重点是啮齿动物和人类之间的物种差异。最后，我们使用单基因骨骼发育不良、内分泌失调和获得性疾病（如佝偻病和股骨头骨骺滑动）作为“自然实验”，阐明了特定的分子扰动如何破坏生长板生理学。总之，这些趋同的证据将生长板重新定义为一个动态的干细胞和祖细胞生态位，其命运是可塑的，高度调控的，并且越来越多地用于治疗线性生长障碍。

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引用次数: 0

Assessment of body composition in active and controlled acromegaly by bioelectrical impedance analysis and dual-energy x-ray absorptiometry 用生物电阻抗分析和双能x线吸收测定法评价主动和控制肢端肥大症患者的身体成分

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2025-12-24 DOI: 10.1016/j.ghir.2025.101678

Signe Graungaard , Mai Christiansen Arlien-Søborg , Niels Henrik Bruun , Erlend Gjersdal , Jens Otto Lunde Jørgensen , Jakob Dal

Purpose

To evaluate the accuracy of bioimpedance analysis (BIA) compared to dual-energy x-ray absorptiometry (DXA) measurements of body composition in patients with active and controlled acromegaly.

Methods

BIA and DXA methods were applied to estimate body composition in patients with active acromegaly and again after disease control.

Results

16 patients with active acromegaly were included and followed until after disease control. GH nadir decreased from 5.5 ± 5.7 μg/L to 0.2 ± 0.3 μg/L, and IGF-1 levels from 565 ± 189 ng/L to 191 ± 137 ng/L after treatment. Body weight remained stable (95.4 ± 30.0 kg and 95.5 ± 26.7 kg) throughout the study period although fat mass increased by 3.2 kg (from 34.1 ± 15.2 kg to 37.5 ± 14.6 kg) or 4.5 kg (31.5 ± 14.6 kg to 36.0 ± 16.0 kg) measured by DXA or BIA, respectively. Lean body mass measured by DXA decreased by 2.2 kg (61.6 ± 16.9 kg to 59.4 ± 14.5 kg), while fat free mass decreased by 4.2 kg (63.4 ± 19.0 kg to 59.2 ± 15.7 kg) and total body water (L) decreased by 3.1 kg (46.4 ± 13.9 kg to 43.3 ± 11.5 kg) estimated by BIA. Using Bland–Altman analysis the bias in estimates for lean mass was −1.7 kg (LOA:−10.0–6.6 kg) in active acromegaly and 0.2 kg (LOA:−10.1–10.5 kg) with hormonal control. For fat mass, bias was 2.6 kg (LOA:−3.8–9.0 kg) in active disease and 1.5 kg (LOA:−5.0–8.1 kg) in controlled disease.

Conclusions

A high conformity between BIA predictions and DXA scan measurements was observed in patients with acromegaly during both active disease and hormonal control. BIA provides additional important estimations of body water content.

目的比较生物阻抗分析（BIA）与双能x线吸收仪（DXA）测量活动性和控制性肢端肥大症患者体成分的准确性。方法应用bia法和DXA法测定活动性肢端肥大症患者的体成分，并在疾病控制后再次测定。结果纳入16例活动性肢端肥大症患者，随访至疾病控制后。治疗后GH最低点由5.5±5.7 μg/L降至0.2±0.3 μg/L， IGF-1水平由565±189 ng/L降至191±137 ng/L。在整个研究期间，体重保持稳定（95.4±30.0 kg和95.5±26.7 kg），尽管DXA或BIA测量的脂肪量分别增加了3.2 kg（从34.1±15.2 kg到37.5±14.6 kg）或4.5 kg（31.5±14.6 kg到36.0±16.0 kg）。DXA测量的瘦体重下降了2.2 kg(61.6±16.9 kg至59.4±14.5 kg)，无脂体重下降了4.2 kg(63.4±19.0 kg至59.2±15.7 kg)， BIA估计的全身水分(L)下降了3.1 kg（46.4±13.9 kg至43.3±11.5 kg）。使用Bland-Altman分析，活动性肢端肥大症患者的瘦体重估计值偏差为- 1.7 kg (LOA: - 10.0-6.6 kg)，激素控制的患者的瘦体重估计值偏差为0.2 kg （LOA: - 10.1-10.5 kg）。对于脂肪质量，活动性疾病的偏差为2.6 kg (LOA:−3.8-9.0 kg)，对照疾病的偏差为1.5 kg （LOA:−5.0-8.1 kg）。结论肢端肥大症患者在活动性疾病和激素控制期间，BIA预测值与DXA扫描值具有较高的符合性。BIA提供了对身体水分含量的额外重要估计。

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引用次数: 0

Safety and efficacy of somapacitan in adults with growth hormone deficiency who were switched from daily growth hormone therapy: A systematic review and meta-analysis somapacitan在从每日生长激素治疗转为生长激素缺乏症的成人中的安全性和有效性：一项系统回顾和荟萃分析

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2025-11-17 DOI: 10.1016/j.ghir.2025.101677

A.B.M. Kamrul-Hasan , Lakshmi Nagendra , Ambika P. Ashraf , Subhankar Chatterjee , Deep Dutta , Joseph M. Pappachan

Background

The safety and efficacy of somapacitan, a novel long-acting growth hormone (GH) formulation, in adults with GH deficiency (GHD) remain insufficiently explored in systematic reviews and meta-analyses (SR/MA). We aimed to fill this knowledge gap.

Methods

Databases were searched to identify RCTs and real-world studies involving adults with GHD who had previously been treated with daily GH and switched to once-weekly somapacitan. The primary outcome was the risk of adverse events (AEs); additional outcomes included treatment satisfaction, body composition measures, and insulin-like growth factor-1 standard deviation scores (IGF-1 SDS).

Results

This SR/MA included five studies (N = 297); four RCTs (n = 286) with a daily GH comparator group were meta-analyzed. Compared to daily GH, somapacitan increased the risk of all AEs (RR 1.31, 95 % CI [1.07, 1.61], P = 0.01), but not the risk of serious AEs or other specific AEs. Glucose homeostasis was less affected by somapacitan, indicated by a lesser increment in HbA1c in the somapacitan group and larger increases in fasting insulin and HOMA-IR in the daily GH group. The convenience score increased more with somapacitan, while effectiveness and satisfaction scores changed similarly in both groups. No differences in body composition changes were observed, but somapacitan improved lumbar spine bone mineral content and density in one study. By the end, IGF-1 SDS values were comparable (MD -0.05 [−0.24, 0.15], P = 0.64).

Conclusion

Somapacitan is as effective as daily GH in treating adults with GHD, with a reasonable safety profile and modest benefits for glucose homeostasis, as well as treatment convenience.

somapacitan是一种新型的长效生长激素（GH）制剂，用于成人GH缺乏症（GHD）的安全性和有效性在系统综述和荟萃分析（SR/MA）中尚未得到充分的探讨。我们的目标是填补这一知识空白。方法检索数据库，以确定随机对照试验和现实世界的研究，这些研究涉及以前每天接受GH治疗的成人GHD患者，然后改为每周一次的somapacitan。主要结局是不良事件（ae）的风险；其他结果包括治疗满意度、体成分测量和胰岛素样生长因子-1标准偏差评分（IGF-1 SDS）。结果本次SR/MA纳入5项研究（N = 297）；4项rct （n = 286）与每日GH比较组进行meta分析。与每日GH相比，somapacitan增加了所有ae的风险（RR 1.31, 95% CI [1.07, 1.61], P = 0.01），但没有增加严重ae或其他特定ae的风险。葡萄糖稳态受somapacitan的影响较小，表明somapacitan组HbA1c的增量较小，而每日GH组空腹胰岛素和HOMA-IR的增加较大。使用somapacitan后，便利性得分增加更多，而两组的有效性和满意度得分变化相似。在一项研究中，没有观察到身体成分变化的差异，但somapacitan改善了腰椎骨矿物质含量和密度。最后，IGF-1 SDS值具有可比性（MD = -0.05 [- 0.24, 0.15], P = 0.64）。结论somapacitan治疗成人GHD与每日GH一样有效，具有合理的安全性和适度的葡萄糖稳态益处，并且治疗方便。

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引用次数: 0

Growth hormone - releasing hormone antagonists induce autophagy in cancer cells 生长激素释放激素拮抗剂诱导癌细胞自噬

IF 1.6 4区医学 Q4 CELL BIOLOGY

Growth Hormone & Igf Research

Pub Date : 2025-10-01 DOI: 10.1016/j.ghir.2025.101668

Madan Sigdel , Saikat Fakir , Md Matiur Rahman Sarker, Nektarios Barabutis

GHRH antagonists (GHRHAnt) were developed to suppress cancers and have been associated with robust anti-inflammatory and anti-oxidative activities. The mechanisms involved in those effects are not completely understood. MDA-MB-468 and A549 cancer cells, which express GHRH receptors, were treated with GHRHAnt JV-1-36, to evaluate the effects of that compound in autophagy. JV-1-36 induces autophagy in MDA-MB-468 and A549 cells since exposure to the aforementioned peptide elevated the expression levels of the autophagy-related protein (ATG) – 5, ATG – 3, ATG – 7, and ATG-16L1. In contrast, MCF-7 cells - which do not express GHRH receptors – did not respond to GHRHAnt. Our findings suggest that the beneficial effects of GHRHAnt in cancers may involve autophagy. Further studies will attempt to delineate the underlying mechanisms.

GHRH拮抗剂（GHRHAnt）被开发用于抑制癌症，并具有强大的抗炎和抗氧化活性。这些影响所涉及的机制尚未完全了解。表达GHRH受体的MDA-MB-468和A549癌细胞用GHRHAnt JV-1-36处理，以评估该化合物对自噬的影响。JV-1-36诱导MDA-MB-468和A549细胞自噬，因为暴露于上述肽提高了自噬相关蛋白(ATG) - 5、ATG- 3、ATG- 7和ATG- 16l1的表达水平。相反，不表达GHRH受体的MCF-7细胞对GHRHAnt没有反应。我们的研究结果表明，GHRHAnt在癌症中的有益作用可能与自噬有关。进一步的研究将试图描述潜在的机制。

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 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

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 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

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 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

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 : 2025-09-22 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

{"title":"Effects of insulin-like growth factor-I and Progranulin on a human trophoblast model","authors":"Makoto Osaka, Atsushi Tajima, Satoshi Takemori, Momoe Watanabe, Tohru Morisada, Shinji Tanigaki, Yoichi Kobayashi","doi":"10.1016/j.ghir.2025.101665","DOIUrl":"10.1016/j.ghir.2025.101665","url":null,"abstract":"<div><div>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 (IGF<img>I) 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 IGF<img>I, 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 (<em>P</em> < 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 IGF<img>I. 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.</div><div>(245 words)</div></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"82 ","pages":"Article 101665"},"PeriodicalIF":1.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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 : 2025-09-12 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