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Meta-analysis of MspI derived variants of growth hormone gene associated with milk yield in dairy cattle MspI衍生的与奶牛产奶量相关的生长激素基因变异的meta分析
IF 1.4 4区 医学 Q4 CELL BIOLOGY Pub Date : 2022-04-01 DOI: 10.1016/j.ghir.2022.101459
Yogesh C. Bangar, Ankit Magotra, A.S. Yadav, C.S. Patil

Objective

The present work aimed to obtain common effect sizes for the gene frequency and association of MspI derived variants of growth hormone (GH) gene with milk yield in dairy cows.

Methods

We performed a systematic review and meta-analysis of 35 published studies identified in literature search from 2000 to 2020 (n = 4164). These studies were specific to fragment size (329) for genotypes viz., CC (224, 105 bp), CD (329, 224, 105 bp) and DD (329 bp). Pooled standard mean differences (SMDs) as effect sizes between allele pairs were derived using different genetic models. The heterogeneity between effects sizes across studies was estimated using I2 Index (%).

Results

The common effect size for gene frequency of allele C (224, 105 bp) was significantly (P < 0.05) higher in 2881 Bos taurus/cross cows (0.82; 95% CI: 0.74, 0.89; I2 = 97.81%) than 1283 Bos indicus cows (0.15; 95% CI: 0.12, 0.18; I2 = 71.90%), with overall gene frequency was 0.33 (95% CI: 0.21, 0.46; I2 = 99.29%). Additive (CC vs. DD) and dominant (CC + CD vs. DD) did not revealed significant (P > 0.05) association with milk yield. However, completely over dominant (CC + DD vs. CD) and recessive (CC vs. CD + DD) models showed significant (P < 0.05) and positive SMDs with milk yield specially at early lactations. There was no evidence of heterogeneity (I2 = 0.00%) between SMDs across studies.

Conclusions

This meta-analysis suggested potential association of C allele for enhancing milk production of dairy cows.

目的研究奶牛生长激素(GH)基因MspI衍生变异的基因频率及其与产奶量的关系。方法:我们对2000年至2020年文献检索中已发表的35项研究(n = 4164)进行了系统回顾和荟萃分析。这些研究是针对基因型的片段大小(329)进行的,即CC (224, 105 bp), CD (329, 224, 105 bp)和DD (329 bp)。利用不同的遗传模型推导出等位基因对间的效应大小。使用I2指数(%)估计各研究间效应大小的异质性。结果等位基因C基因频率的共同效应量(224,105 bp)显著(P <2881头牛/杂交牛(0.82;95% ci: 0.74, 0.89;I2 = 97.81%)高于1283头母牛(0.15;95% ci: 0.12, 0.18;I2 = 71.90%),总基因频率为0.33 (95% CI: 0.21, 0.46;i2 = 99.29%)。加性(CC vs. DD)和显性(CC + CD vs. DD)无显著差异(P >0.05)与产奶量相关。然而,完全过显性(CC + DD vs. CD)和隐性(CC vs. CD + DD)模型显示显著(P <0.05), smd阳性与泌乳量有关,尤其是在泌乳早期。没有证据表明不同研究的smd之间存在异质性(I2 = 0.00%)。结论本荟萃分析提示C等位基因与奶牛产奶量的潜在关联。
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引用次数: 0
The role of growth hormone for fertility in women with hypopituitarism 生长激素在垂体功能低下妇女生育中的作用
IF 1.4 4区 医学 Q4 CELL BIOLOGY Pub Date : 2022-04-01 DOI: 10.1016/j.ghir.2022.101458
Julie Chen , Laurence Katznelson

Growth hormone (GH) is an important regulator of the female reproductive system. In vitro and non-human in vivo studies demonstrate a role of GH in steroidogenesis, folliculogenesis, and post-fertilization development. Given its ability to modulate the reproductive system and potentiate the effects of gonadotropins, a beneficial role of GH replacement therapy to optimize fertility has been suggested. Women with hypopituitarism have lower pregnancy and live birth rates. Limited data suggest a role of GH in enhancing fertility management in women with hypopituitarism. GH replacement therapy may be especially relevant in women with hypopituitarism as well as in women considered poor ovarian responders and require assisted reproductive techniques.

生长激素(GH)是女性生殖系统的重要调节因子。体外和非人类体内研究表明生长激素在类固醇生成、卵泡生成和受精后发育中的作用。鉴于其调节生殖系统和增强促性腺激素作用的能力,已经提出了生长激素替代疗法在优化生育能力方面的有益作用。垂体功能减退的妇女怀孕率和活产率较低。有限的数据表明生长激素在增强垂体功能低下妇女生育管理中的作用。生长激素替代疗法可能特别适用于垂体功能低下的妇女,以及被认为卵巢反应不良和需要辅助生殖技术的妇女。
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引用次数: 0
Liver and muscle-specific effects of phoenixin-20 on the insulin-like growth factor system mRNAs in zebrafish 凤凰素-20对斑马鱼胰岛素样生长因子系统mrna的肝脏和肌肉特异性影响
IF 1.4 4区 医学 Q4 CELL BIOLOGY Pub Date : 2022-04-01 DOI: 10.1016/j.ghir.2022.101456
Jithine Jayakumar Rajeswari , Emilio J. Vélez , Suraj Unniappan

Objective

Phoenixin-20 (Pnx-20) is a bioactive peptide with endocrine-like actions in vertebrates. Recent studies suggest Pnx-20 promotes growth hormone/insulin-like growth factors (Gh/Igf) axis, an important endocrine regulator of growth in mammals and fish.

Design

In this research, we determined whether Pnx-20 affects the different members of the Igf family, its binding proteins and receptors (Igf-system) in zebrafish liver and muscle.

Results

In vivo administration of Pnx-20 downregulated igfs, igf receptors (igfrs) and igf binding protein (igfbp) 5 mRNA expression in the liver of male and female zebrafish at both 1 and 6 h post-intraperitoneal (IP) injection. Interestingly, this effect occurred at a relatively earlier timepoint in female zebrafish suggesting sex-specific differences in Pnx-20 action. Besides, either 6 or 24 h in vitro incubations with Pnx-20 downregulated the expression of all igfs, igfrs and igfbp5 mRNAs (except igf2a) analyzed in a zebrafish liver cell (ZFL) line. Moreover, siRNA-mediated knockdown of Pnx-20 upregulated all Igf-system mRNAs analyzed in ZFL cells. Together, these results (both in vivo and in vitro) revealed a general suppressive action for both endogenous and exogenous Pnx-20 on the hepatic Igf-system of zebrafish. In contrast, a general sex-specific upregulation of the Igf-system mRNAs analyzed was found in the muscle of Pnx-20 injected fish. Future research should explore the sex- and time-differences observed in the present study.

Conclusions

Collectively, this research shows that Pnx-20 is a tissue-specific regulator of the liver (suppressor) and muscle (stimulant) Igf signaling in both male and female zebrafish.

目的研究凤凰素-20 (phoenixin -20, Pnx-20)是一种具有内分泌样作用的生物活性肽。最近的研究表明,Pnx-20促进生长激素/胰岛素样生长因子(Gh/Igf)轴,这是哺乳动物和鱼类生长的重要内分泌调节因子。在本研究中,我们确定了Pnx-20是否影响斑马鱼肝脏和肌肉中Igf家族的不同成员、其结合蛋白和受体(Igf系统)。结果Pnx-20在腹腔注射后1和6 h下调雄性和雌性斑马鱼肝脏中igfs、igf受体(igfrs)和igf结合蛋白(igfbp) 5mrna的表达。有趣的是,这种效应发生在雌性斑马鱼相对较早的时间点,这表明Pnx-20的作用存在性别特异性差异。此外,Pnx-20体外培养6或24小时后,斑马鱼肝细胞(ZFL)中除igf2a外,所有igfs、igfrs和igfbp5 mrna的表达均下调。此外,sirna介导的Pnx-20的下调上调了ZFL细胞中分析的所有igf系统mrna。总之,这些结果(体内和体外)揭示了内源性和外源性Pnx-20对斑马鱼肝脏igf系统的普遍抑制作用。相比之下,在注射Pnx-20的鱼的肌肉中发现了igf系统mrna的性别特异性上调。未来的研究应该探索在本研究中观察到的性别和时间差异。总之,本研究表明Pnx-20在雄性和雌性斑马鱼中都是肝脏(抑制因子)和肌肉(刺激因子)Igf信号的组织特异性调节因子。
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引用次数: 1
The true story of the “strong and gentle” Acciano's Giant “坚强而温柔”的阿齐亚诺的巨人的真实故事
IF 1.4 4区 医学 Q4 CELL BIOLOGY Pub Date : 2022-04-01 DOI: 10.1016/j.ghir.2022.101457
Maria Maddalena Sirufo , Lina Maria Magnanimi , Lia Ginaldi , Massimo De Martinis

This is the story of a giant who lived in Abruzzo 200 years ago. He became a symbol for his people and a strong resilience generator. Gigantism, in the history of humanity has always attracted attention, albeit passing over the centuries from myth, from divinity to the freak phenomenon, the freak of nature that becomes a spectacle to show off. The attraction for understanding the pathophysiological mechanisms underlying gigantism developed by the end of 19th century. Increased levels of growth hormone (GH) or insulin-like growth hormone 1 (IGF1) causes overgrowth in pituitary gigantism. The imposing size of the body, in our imagination, represents strength and health, reason why in our imagination it almost becomes a divine mythical image. The story of the Acciano's Giant represents a cultural heritage that passes from one generation to the next, that contributes in giving a sense of identity and continuity. It provides a link from past to present and to the future. Encourages a sense of identity and responsibility contributing to social cohesion, helping individuals to feel members of one community. A disease, represented by the Giant, has become a symbol capable of bringing the community together and giving it the strength to react to environment, nature and history. This is a lesson that teaches us the sense of community.

这是200年前住在阿布鲁佐的一个巨人的故事。他成为了他的人民的象征,一个强大的恢复力发电机。巨人症,在人类历史上一直吸引着人们的注意,尽管经历了几个世纪,从神话,从神性到怪异的现象,自然的怪异,成为炫耀的奇观。对巨人症的病理生理机制的理解是在19世纪末发展起来的。生长激素(GH)或胰岛素样生长激素1 (IGF1)水平升高导致垂体巨人症过度生长。在我们的想象中,雄伟的身躯代表着力量和健康,这就是为什么在我们的想象中,它几乎成为一个神圣的神话形象。阿齐亚诺的《巨人》的故事代表了一种文化遗产,从一代传到下一代,这有助于给人一种认同感和连续性。它提供了从过去到现在和到未来的联系。鼓励认同感和责任感,有助于社会凝聚力,帮助个人感觉自己是一个社区的成员。一种疾病,以巨人为代表,已经成为一种象征,能够将社区团结在一起,并赋予它应对环境、自然和历史的力量。这是教会我们社区意识的一课。
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引用次数: 0
Hormonal, metabolic, and angiogenic responses to all-out sprint interval exercise under systemic hyperoxia 全身性高氧条件下全速冲刺间歇运动的激素、代谢和血管生成反应
IF 1.4 4区 医学 Q4 CELL BIOLOGY Pub Date : 2022-04-01 DOI: 10.1016/j.ghir.2022.101445
Michihiro Kon , Yoshiko Ebi , Kohei Nakagaki

Objective

Hyperoxic gas inhalation during exercise may negatively affect all-out sprint interval exercise (SIE)-induced hormonal, metabolic, and angiogenic responses. We investigated the effects of acute all-out SIE under systemic hyperoxia on hormonal, metabolic, and angiogenic responses.

Design

This was a randomised-crossover trial. Ten healthy males (mean ± standard error of age = 23.1 ± 0.9 years; height = 171.0 ± 1.6 cm; body mass = 66.2 ± 2.0 kg; body mass index = 22.6 ± 0.5 kg/m2) completed the following two experimental regimens: 1) SIE under normoxia and 2) SIE under systemic hyperoxia (FiO2 = 60%). The subjects performed four bouts of 30-s maximal cycling efforts with 4 min recovery between efforts. The circulating levels of hormonal (growth hormone, epinephrine, and norepinephrine), metabolic (glucose, free fatty acid, and lactate), and angiogenic (vascular endothelial growth factor, matrix metalloproteinase-2 and -9, and endostatin) markers were measured before and at 0 (immediately after the regimen), 30, and 120 min after both regimens.

Results

In response to both SIE regimens, the peak and mean power outputs gradually decreased over the intermittent exercise session compared with those in the first bout (p < 0.01) with no significant differences between the regimens. Both regimens significantly increased the circulating concentrations of all hormonal, metabolic, and angiogenic markers (p < 0.01). However, there were no significant differences in the levels of these markers in response to the two regimens at any time point (p > 0.05).

Conclusion

These findings suggest that acute systemic hyperoxia does not influence the hormonal, metabolic, and angiogenic responses to all-out SIE.

目的运动时高氧气体吸入可能对全速冲刺间歇运动(SIE)诱导的激素、代谢和血管生成反应产生负面影响。我们研究了全身高氧条件下急性全面SIE对激素、代谢和血管生成反应的影响。这是一项随机交叉试验。健康男性10例(年龄平均±标准误差= 23.1±0.9岁;高度= 171.0±1.6 cm;体重= 66.2±2.0 kg;体重指数= 22.6±0.5 kg/m2)完成了两个实验方案:1)常氧下SIE和2)全身高氧(FiO2 = 60%)下SIE。受试者进行了四组30秒的最大自行车运动,每次运动之间的恢复时间为4分钟。在两种治疗方案开始前和治疗后0分钟(治疗后立即)、30分钟和120分钟测量激素(生长激素、肾上腺素和去甲肾上腺素)、代谢(葡萄糖、游离脂肪酸和乳酸)和血管生成(血管内皮生长因子、基质金属蛋白酶-2和-9、内皮抑素)标志物的循环水平。结果在两种SIE方案的反应中,间歇运动期间的峰值和平均功率输出与第一回合相比逐渐下降(p <0.01),两组间无显著差异。两种方案都显著增加了所有激素、代谢和血管生成标志物的循环浓度(p <0.01)。然而,在两种方案的任何时间点,这些标志物的水平没有显著差异(p >0.05)。结论急性全身性高氧不影响全负荷SIE的激素、代谢和血管生成反应。
{"title":"Hormonal, metabolic, and angiogenic responses to all-out sprint interval exercise under systemic hyperoxia","authors":"Michihiro Kon ,&nbsp;Yoshiko Ebi ,&nbsp;Kohei Nakagaki","doi":"10.1016/j.ghir.2022.101445","DOIUrl":"10.1016/j.ghir.2022.101445","url":null,"abstract":"<div><h3>Objective</h3><p>Hyperoxic gas inhalation during exercise may negatively affect all-out sprint interval exercise (SIE)-induced hormonal, metabolic, and angiogenic responses. We investigated the effects of acute all-out SIE under systemic hyperoxia on hormonal, metabolic, and angiogenic responses.</p></div><div><h3>Design</h3><p><span>This was a randomised-crossover trial. Ten healthy males (mean ± standard error of age = 23.1 ± 0.9 years; height = 171.0 ± 1.6 cm; body mass = 66.2 ± 2.0 kg; body mass index = 22.6 ± 0.5 kg/m</span><sup>2</sup>) completed the following two experimental regimens: 1) SIE under normoxia and 2) SIE under systemic hyperoxia (FiO<sub>2</sub><span> = 60%). The subjects performed four bouts of 30-s maximal cycling efforts with 4 min recovery between efforts. The circulating levels of hormonal (growth hormone, epinephrine, and norepinephrine), metabolic (glucose, free fatty acid, and lactate), and angiogenic (vascular endothelial growth factor, matrix metalloproteinase-2 and -9, and endostatin) markers were measured before and at 0 (immediately after the regimen), 30, and 120 min after both regimens.</span></p></div><div><h3>Results</h3><p>In response to both SIE regimens, the peak and mean power outputs gradually decreased over the intermittent exercise session compared with those in the first bout (p &lt; 0.01) with no significant differences between the regimens. Both regimens significantly increased the circulating concentrations of all hormonal, metabolic, and angiogenic markers (p &lt; 0.01). However, there were no significant differences in the levels of these markers in response to the two regimens at any time point (p &gt; 0.05).</p></div><div><h3>Conclusion</h3><p>These findings suggest that acute systemic hyperoxia does not influence the hormonal, metabolic, and angiogenic responses to all-out SIE.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"63 ","pages":"Article 101445"},"PeriodicalIF":1.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39926431","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
Effects of high-dose all-trans retinoic acid on longitudinal bone growth of young rats 大剂量全反式维甲酸对幼鼠纵向骨生长的影响
IF 1.4 4区 医学 Q4 CELL BIOLOGY Pub Date : 2022-02-01 DOI: 10.1016/j.ghir.2022.101446
Qin Shen , Xia Wang , Haodi Bai , Xin Tan , Xing Liu

Objective

The signaling axis consisting of GH-IGF1-IGFBP3 is the primary signal taht acts prepubertally to influence height development. Growth plate thinning and even premature closure have been reported in children with tumors treated with retinoid chemotherapy, resulting in long bone dysplasia. Growth failure may occur despite received GH treatment, but the reason is unknown. This study investigate the effect of high-dose all-trans retinoic acid (ATRA) on the development of long bones in growing SD rats.

Methods

A total of 20 three-week-old male SD rats were randomly divided into a control group and an experimental group (n = 10). Rats were treated by gavage with or without high-dose ATRA for 10 days. The body weights of the rats were recorded daily. At the end of the experiment, we measured the length of nose-tail and tibia, stained the tibia and liver for pathological tissue and RT-PCR reaction, and measured the levels of serum GH, IGF1 and IGFBP3, and so on.

Results

Compared with controls, experimental rats exhibited reduced body weight and shortened nasal-tail and radial tibial length. Cyp26b1 enzyme activity in the liver was elevated, and histopathological staining revealed that the cartilaginous epiphyseal plate was narrowed, the medullary cavity of trabecular bone was sparse, the number of trabecular bones was decreased, trabecular separation was increased, bone marrow mineralization was enhanced, osteoclastic activity was increased, and circulating GH-IGF1-IGFBP3 levels were decreased. However, RT-PCR reaction results of localized proximal tibiae showed upregulation of IGF1 and downregulation of IGFBP3.

Conclusions

High-dose ATRA intake over a short period of time can reduce GH-IGF1-IGFBP3 levels, affect cartilage and bone homeostasis, and inhibit bone growth in developing animals.

目的GH-IGF1-IGFBP3信号轴是青春期前影响身高发育的主要信号。有报道称,在接受类维甲酸化疗的儿童肿瘤中,生长板变薄甚至过早闭合,导致长骨发育不良。尽管接受生长激素治疗,仍可能发生生长衰竭,但原因尚不清楚。本研究探讨了大剂量全反式维甲酸(ATRA)对生长SD大鼠长骨发育的影响。方法选用3周龄雄性SD大鼠20只,随机分为对照组和试验组(n = 10)。大鼠分别给予或不给予高剂量ATRA灌胃10 d。每天记录大鼠体重。实验结束后测量鼻尾和胫骨长度,对胫骨和肝脏进行病理组织染色和RT-PCR反应,测定血清GH、IGF1、IGFBP3水平等。结果与对照组相比,实验组大鼠体重减轻,鼻尾和桡胫长度缩短。肝脏Cyp26b1酶活性升高,组织病理学染色显示软骨骺板变窄,骨小梁髓腔稀疏,骨小梁数量减少,骨小梁分离增加,骨髓矿化增强,破骨活性增加,循环GH-IGF1-IGFBP3水平降低。然而,局部胫骨近端RT-PCR反应结果显示IGF1上调,IGFBP3下调。结论短时间内摄入高剂量ATRA可降低发育动物GH-IGF1-IGFBP3水平,影响软骨和骨骼稳态,抑制骨骼生长。
{"title":"Effects of high-dose all-trans retinoic acid on longitudinal bone growth of young rats","authors":"Qin Shen ,&nbsp;Xia Wang ,&nbsp;Haodi Bai ,&nbsp;Xin Tan ,&nbsp;Xing Liu","doi":"10.1016/j.ghir.2022.101446","DOIUrl":"10.1016/j.ghir.2022.101446","url":null,"abstract":"<div><h3>Objective</h3><p>The signaling axis consisting of GH-IGF1-IGFBP3 is the primary signal taht acts prepubertally to influence height development. Growth plate<span><span><span><span> thinning and even premature closure have been reported in children with tumors treated with retinoid chemotherapy, resulting in long </span>bone dysplasia. Growth failure may occur despite received GH </span>treatment<span>, but the reason is unknown. This study investigate the effect of high-dose all-trans retinoic acid (ATRA) on the development of long bones in growing </span></span>SD rats.</span></p></div><div><h3>Methods</h3><p>A total of 20 three-week-old male SD rats were randomly divided into a control group and an experimental group (<em>n</em><span> = 10). Rats were treated by gavage with or without high-dose ATRA for 10 days. The body weights of the rats were recorded daily. At the end of the experiment, we measured the length of nose-tail and tibia<span>, stained the tibia and liver for pathological tissue<span><span> and RT-PCR reaction, and measured the levels of serum GH, IGF1 and </span>IGFBP3, and so on.</span></span></span></p></div><div><h3>Results</h3><p>Compared with controls, experimental rats exhibited reduced body weight and shortened nasal-tail and radial tibial length. Cyp26b1 enzyme activity<span><span><span> in the liver was elevated, and histopathological staining revealed that the cartilaginous epiphyseal plate was narrowed, the medullary cavity of trabecular bone was sparse, the number of trabecular bones was decreased, trabecular separation was increased, bone marrow </span>mineralization was enhanced, osteoclastic activity was increased, and circulating GH-IGF1-IGFBP3 levels were decreased. However, RT-PCR reaction results of localized </span>proximal tibiae showed upregulation of IGF1 and downregulation of IGFBP3.</span></p></div><div><h3>Conclusions</h3><p>High-dose ATRA intake over a short period of time can reduce GH-IGF1-IGFBP3 levels, affect cartilage and bone homeostasis, and inhibit bone growth in developing animals.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"62 ","pages":"Article 101446"},"PeriodicalIF":1.4,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39911457","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: 4
Dental arches in inherited severe isolated growth hormone deficiency 遗传性严重分离生长激素缺乏症的牙弓
IF 1.4 4区 医学 Q4 CELL BIOLOGY Pub Date : 2022-02-01 DOI: 10.1016/j.ghir.2022.101444
Rafaela S. Girão , Manuel H. Aguiar-Oliveira , Bruna M.R. Andrade , Marcos A.V. Bittencourt , Roberto Salvatori , Evânio V. Silva , André L.M. Santos , Matheus M. Cunha , Wilton M. Takeshita , Alaíde H.A. Oliveira , Eugênia H.O. Valença , Alécia A. Oliveira-Santos , Luiz A. Oliveira-Neto

Objectives

The growth of the dental arches depends on GH and insulin-like growth factor type 1 (IGF1), but the consequences of GH deficiency (GHD) on their growth are still unclear, probably due to the acquired etiology of GHD in most described series, often associated with additional pituitary deficits (thyrotrophic, corticotrophic and gonadotrophic hormones), and imperfections of related replacement therapies, which may affect the dental arch growth. To avoid these limitations, we took advantage of a unique cohort of subjects with isolated GH deficiency (IGHD) due the same mutation in the GH releasing hormone receptor gene, living with very low serum GH and low to undetectable circulating IGF1 levels. Our purpose was to analyze the dimensions of maxillary and mandibular dental arches.

Methods

22 adult IGHD (15 untreated and 7 previously partially treated with GH) and 33 controls were enrolled in a cross-sectional study using the Ortho Insight 3D and MeshMixer software,

Results

In untreated IGHD subjects all maxillary arch measures were smaller than controls, while among mandibular arches, only the mandibular canine width and the mandibular arch length were reduced. In partially GH treated subjects only the palate depth, the maxillary canine width, the maxillary and mandibular arch lengths remained smaller than controls.

Conclusions

IGHD reduces the growth of maxillary arch to a greater degree than the mandibular arch, suggesting different control of superior and inferior dental arches. GH treatment increases some of these measures.

目的牙弓的生长依赖于生长激素和胰岛素样生长因子1型(IGF1),但生长激素缺乏(GHD)对牙弓生长的影响尚不清楚,可能是由于大多数描述的GHD的获得性病因,通常与额外的垂体缺陷(甲状腺、促皮质和促性腺激素)以及相关替代疗法的不完善有关,这可能会影响牙弓的生长。为了避免这些局限性,我们利用了一组独特的研究对象,这些研究对象是由于生长激素释放激素受体基因的相同突变而孤立的生长激素缺乏症(IGHD),他们的血清生长激素非常低,循环IGF1水平低到无法检测。我们的目的是分析上颌和下颌牙弓的尺寸。方法采用Ortho Insight 3D和MeshMixer软件对22名成人IGHD患者(15名未治疗,7名曾部分接受GH治疗)和33名对照组进行横断面研究。结果未治疗的IGHD患者上颌弓的测量值均小于对照组,而在下颌弓中,只有下颌犬齿宽度和下颌弓长度减小。在部分GH治疗的受试者中,只有上颚深度、上颌犬齿宽度、上颌和下颌弓长度比对照组小。结论sigd对上颌弓生长的抑制作用大于对下颌骨弓生长的抑制作用,说明对上下牙弓的控制是不同的。生长激素治疗增加了这些措施中的一些。
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引用次数: 4
Regulation of 11β-HSD1 by GH/IGF-1 in key metabolic tissues may contribute to metabolic disease in GH deficient patients GH/IGF-1在关键代谢组织中调控11β-HSD1可能有助于GH缺乏患者的代谢性疾病
IF 1.4 4区 医学 Q4 CELL BIOLOGY Pub Date : 2022-02-01 DOI: 10.1016/j.ghir.2021.101440
Stuart A. Morgan , Darlene E. Berryman , Edward O. List , Gareth G. Lavery , Paul M. Stewart , John J. Kopchick

Patients with growth hormone deficiency (GHD) have many clinical features in common with Cushing's syndrome (glucocorticoid excess) – notably visceral obesity, insulin resistance, muscle myopathy and increased vascular mortality. Within key metabolic tissues, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts cortisone to the active glucocorticoid, cortisol (11-dehydrocorticosterone and corticosterone in rodents respectively), and thus amplifies local glucocorticoid action.

We hypothesize that 11β-HSD1 expression is negatively regulated by growth hormone (GH), and that GHD patients have elevated 11β-HSD1 within key metabolic tissues (leading to increased intracellular cortisol generation) which contributes to the clinical features of this disease.

To identify the impact of GH excess/resistance on 11β-HSD1 in vivo, we measured mRNA expression in key metabolic tissues of giant mice expressing the bovine GH (bGH) gene, dwarf mice with a disrupted GH receptor (GHRKO) gene and mice expressing a gene encoding a GH receptor antagonist (GHA). Additionally, we assessed urine steroid markers of 11β-HSD1 activity in both GHRKO and bGH animals.

11β-HSD1 expression was decreased in gastrocnemius muscle (0.43-fold, p < 0.05), subcutaneous adipose (0.53-fold, p < 0.05) and epididymal adipose tissue (0.40-fold, p < 0.05), but not liver, in bGH mice compared to WT controls. This was paralleled by an increased percentage of 11-DHC (inactive glucocorticoid) present in the urine of bGH mice compared to WT controls (2.5-fold, p < 0.01) - consistent with decreased systemic 11β-HSD1 activity. By contrast, expression of 11β-HSD1 was increased in the liver of GHRKO (2.7-fold, p < 0.05) and GHA mice (2.0-fold, p < 0.05) compared to WT controls, but not gastrocnemius muscle, subcutaneous adipose tissue or epididymal adipose tissue.

In summary, we have demonstrated a negative relationship between GH action and 11β-HSD1 expression which appears to be tissue specific. These data provide evidence that increased intracellular cortisol production within key tissues may contribute to metabolic disease in GHD patients.

生长激素缺乏症(GHD)患者与库欣综合征(糖皮质激素过量)有许多共同的临床特征——尤其是内脏肥胖、胰岛素抵抗、肌肉肌病和血管死亡率增加。在关键代谢组织中,11β-羟基类固醇脱氢酶1型(11β-HSD1)将可的松转化为活性糖皮质激素皮质醇(啮齿动物分别为11-脱氢皮质酮和皮质酮),从而增强局部糖皮质激素的作用。我们假设11β-HSD1的表达受到生长激素(GH)的负调控,GHD患者在关键代谢组织中11β-HSD1升高(导致细胞内皮质醇生成增加),这有助于该疾病的临床特征。为了确定生长激素过量/抵抗对体内11β-HSD1的影响,我们测量了表达牛生长激素(bGH)基因的巨型小鼠、生长激素受体(GHRKO)基因中断的侏儒小鼠和表达编码生长激素受体拮抗剂(GHA)基因的小鼠关键代谢组织中的mRNA表达。此外,我们评估了GHRKO和bGH动物尿液中11β-HSD1活性的类固醇标志物。11β-HSD1在腓肠肌中的表达降低(0.43倍,p <0.05),皮下脂肪(0.53倍,p <0.05)和附睾脂肪组织(0.40倍,p <0.05),但与WT对照组相比,bGH小鼠的肝脏没有。与WT对照组相比,bGH小鼠尿液中11-DHC(无活性糖皮质激素)的百分比增加(2.5倍,p <0.01) -与系统11β-HSD1活性降低一致。相比之下,11β-HSD1在GHRKO的肝脏中表达增加(2.7倍,p <0.05)和GHA小鼠(2.0倍,p <0.05),但腓肠肌、皮下脂肪组织或附睾脂肪组织与WT对照组相比无显著差异。总之,我们已经证明了生长激素作用与11β-HSD1表达之间的负相关关系,这似乎是组织特异性的。这些数据提供了关键组织内细胞内皮质醇生成增加可能导致GHD患者代谢性疾病的证据。
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引用次数: 2
Novel gross deletion at the LHX4 gene locus in a child with growth hormone deficiency 生长激素缺乏症儿童LHX4基因位点的新缺失
IF 1.4 4区 医学 Q4 CELL BIOLOGY Pub Date : 2022-02-01 DOI: 10.1016/j.ghir.2021.101443
Saumya Madushani Samarasinghe , Tharmini Sundralingam , Asanka Sudeshini Hewage , K.S.H. de Silva , Kamani Hemamala Tennekoon

Objective

To identify and characterize a novel deletion at the LHX4 gene locus in a proband with growth hormone deficiency (GHD).

Methods

Long range polymerase chain reaction (PCR) amplification was used to confirm the suspected deletion and to identify the rough locations of the end points. Sanger sequencing was carried out to identify the exact end points of the deletion.

Results

Suspected deletion was confirmed via long range PCR amplification. Sanger sequencing identified the end points of the deletion within three nucleotide repeat sequences (“CTT”). The total length of the deleted segment was 12 127 base pairs and it includes complete exon 5 and exon 6 of the LHX4 gene. Therefore the homeodomain motif coded by exons 4 and 5, might be affected.

Conclusion

We have identified a novel deletion that spans exon 5 and exon 6 of the LHX4 gene that could have occurred via microhomology mediated non-recurrent rearrangement. The deletion characterized does not appear to have been reported before. To our knowledge this novel deletion is the first identified LHX4 variant from Sri Lanka and it explains the phenotype of the proband characterized by growth hormone deficiency, hypoplastic anterior pituitary and subsequent deficiency of thyroid stimulating hormone and adrenocorticotropic hormone (ACTH).

目的鉴定生长激素缺乏症(GHD)先证者LHX4基因缺失的新特征。方法采用远程聚合酶链反应(PCR)扩增技术对疑似缺失的基因进行确证,并确定基因末端的大致位置。进行Sanger测序以确定缺失的确切终点。结果通过长距离PCR扩增证实了怀疑缺失。Sanger测序在三个核苷酸重复序列(“CTT”)内确定了缺失的终点。缺失片段全长12 127个碱基对,包含LHX4基因完整的外显子5和外显子6。因此,由外显子4和5编码的同源结构域基序可能受到影响。结论我们发现了LHX4基因外显子5和外显子6的一个新的缺失,可能是通过微同源介导的非复发性重排发生的。这种缺失特征似乎以前没有报道过。据我们所知,这一新的缺失是斯里兰卡首次发现的LHX4变异,它解释了先证者以生长激素缺乏、垂体前叶发育不全以及随后的促甲状腺激素和促肾上腺皮质激素(ACTH)缺乏为特征的表型。
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引用次数: 0
Personality traits in acromegalic patients: Comparison with patients with non-functioning adenomas and healthy controls 肢端肥大症患者的人格特征:与无功能腺瘤患者和健康对照的比较
IF 1.4 4区 医学 Q4 CELL BIOLOGY Pub Date : 2022-02-01 DOI: 10.1016/j.ghir.2021.101439
Elif Kilic Kan , Aysegul Atmaca , Gokhan Sarisoy , Gulcin Cengiz Ecemis , Feyzi Gokosmanoglu

Objectives

Pituitary diseases may cause psychiatric and personality alterations. We aimed to compare the personality traits of acromegalic patients with those of patients with non-functioning pituitary adenomas and a healthy control group.

Design

Fifty-eight acromegalic patients, 45 patients with non-functioning adenoma, and 40 healthy subjects were enrolled in the study. Cloninger's Temperament and Character Inventory (TCI), Beck Depression Inventory, Beck Anxiety Inventory, and Rosenberg Self-Esteem Scale (RSES) were used to assess personality, depression, anxiety, and self-esteem.

Results

Depression score was higher in acromegaly and non-functioning adenoma groups than healthy controls. RSES scores were similar among the three groups. Regarding the scales of TCI, only novelty-seeking was significantly reduced in acromegaly and non-functioning adenoma than the control group. Pairwise comparisons revealed that the difference was due to the difference between acromegalic patients and controls. Scales of TCI were correlated with depression and anxiety in patients with acromegaly and non-functioning adenoma but not in healthy controls.

Conclusion

This study showed that novelty-seeking was reduced in patients with acromegaly. Both the hormonal lack and excess and structural changes can lead to cognitive and personality changes in acromegaly. More studies are needed to be carried out about personality characteristics in pituitary diseases.

目的:肺脏疾病可引起精神和人格改变。我们的目的是比较肢端肥大症患者与无功能垂体腺瘤患者和健康对照组的人格特征。58名肢端肥大症患者、45名无功能腺瘤患者和40名健康受试者被纳入研究。采用Cloninger气质与性格量表(TCI)、Beck抑郁量表、Beck焦虑量表和Rosenberg自尊量表(RSES)评估人格、抑郁、焦虑和自尊。结果肢端肥大症和无功能腺瘤组抑郁评分高于健康对照组。三组患者的RSES评分相似。在TCI量表方面,只有肢端肥大症和无功能腺瘤患者寻求新奇性明显低于对照组。两两比较显示,差异是由于肢端肥大症患者和对照组之间的差异。肢端肥大症和无功能腺瘤患者的TCI量表与抑郁和焦虑相关,但在健康对照中无相关。结论肢端肥大症患者的求新行为有所减少。肢端肥大症患者的激素缺乏和过量以及结构变化都可能导致认知和人格改变。垂体疾病患者的人格特征有待进一步研究。
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引用次数: 3
期刊
Growth Hormone & Igf Research
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