Different thresholds of tissue-specific dose-responses to growth hormone in short prepubertal children

Decker, Ralph; Nygren, Anders; Kriström, Berit; Nierop, Andreas F M; Gustafsson, Jan Åke; Albertsson‐Wikland, Kerstin; Dahlgren, Jovanna

doi:10.1186/1472-6823-12-26

Cited by 12 publications

(7 citation statements)

References 44 publications

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“…The higher impact of combined treatment on body weight and organ growth could be related to different tissue responsiveness to IGF-I affecting the outcome or efficacy of a given dose. Such dose-dependent, differential thresholds for biological effects have been suggested for GH treatment (44). Alternatively, one can speculate different degrees of fluid retention where an avascular tissue like the GP is less susceptible to extravasation of fluid than other, vascularized and more loosely packed, tissues.…”

Section: Discussionmentioning

confidence: 96%

Combined Treatment With GH and IGF-I: Additive Effect on Cortical Bone Mass But Not on Linear Bone Growth in Female Rats

et al. 2014

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The growth-promoting effect of combined therapy with GH and IGF-I in normal rats is not known. We therefore investigated the efficacy of treatment with recombinant human (rh)GH and/or rhIGF-I on longitudinal bone growth and bone mass in intact, prepubertal, female Sprague-Dawley rats. rhGH was injected twice daily sc (5 mg/kg·d) and rhIGF-I continuously infused sc (2.2 or 4.4 mg/kg·d) for 28 days. Longitudinal bone growth was monitored by weekly x-rays of tibiae and nose-anus length measurements, and tibial growth plate histomorphology was analyzed. Bone mass was evaluated by peripheral quantitative computed tomography. In addition, serum levels of IGF-I, rat GH, acid labile subunit, IGF binding protein-3, 150-kDa ternary complex formation, and markers of bone formation and degradation were measured. Monotherapy with rhGH was more effective than rhIGF-I (4.4 mg/kg·d) to increase tibia and nose-anus length, whereas combined therapy did not further increase tibia, or nose-anus, lengths or growth plate height. In contrast, combined rhGH and rhIGF-I (4.4 mg/kg·d) therapy had an additive stimulatory effect on cortical bone mass vs rhGH alone. Combined treatment with rhGH and rhIGF-I resulted in markedly higher serum IGF-I concentrations vs rhGH alone but did not compromise the endogenous secretion of GH. We conclude that rhIGF-I treatment augments cortical bone mass but does not further improve bone growth in rhGH-treated young, intact, female rats.

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Section: Discussionmentioning

confidence: 96%

Combined Treatment With GH and IGF-I: Additive Effect on Cortical Bone Mass But Not on Linear Bone Growth in Female Rats

et al. 2014

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“…GH/IGF-I responsiveness varies not only between individuals but also between tissues within an individual, e.g. more GH is needed to produce an effect on IGF-I production than for longitudinal bone growth [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Growth hormone (GH) dose-dependent IGF-I response relates to pubertal height gain

et al. 2015

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BackgroundResponsiveness to GH treatment can be estimated by both growth and ∆IGF-I. The primary aim of the present study was to investigate if mimicking the physiological increase during puberty in GH secretion, by using a higher GH dose could lead to pubertal IGFs in short children with low GH secretion. The secondary aim was to explore the relationship between IGF-I, IGFBP-3 and the IGF-I/IGFBP-3 ratio and gain in height.MethodsA multicentre, randomized, clinical trial (TRN88-177) in 104 children (90 boys), who had received GH 33 μg/kg/day during at least 1 prepubertal year. They were followed from GH start to adult height (mean, 7.5 years; range, 4.6–10.7). At onset of puberty, children were randomized into three groups, to receive 67 μg/kg/day (GH67) given once (GH67x1; n = 30) or divided into two daily injection (GH33x2; n = 36), or to remain on a single 33 μg/kg/day dose (GH33x1; n = 38). The outcome measures were change and obtained mean on-treatment IGF-ISDS, IGFBP3SDS and IGF-I/IGFBP3 ratioSDS during prepuberty and puberty. These variables were assessed in relation to prepubertal, pubertal and total gain in heightSDS.ResultsMean prepubertal increases 1 year after GH start were: 2.1 IGF-ISDS, 0.6 IGFBP3SDS and 1.5 IGF-I/IGFBP3ratioSDS. A significant positive correlation was found between prepubertal ∆IGFs and both prepubertal and total gain in heightSDS. During puberty changes in IGFs were GH dose-dependent: mean pubertal level of IGF-ISDS was higher in GH67 vs GH33 (p = 0.031). First year pubertal ∆IGF-ISDS was significantly higher in the GH67vs GH33 group (0.5 vs −0.1, respectively, p = 0.007), as well as ∆IGF-ISDS to the pubertal mean level (0.2 vs −0.2, p = 0.028). In multivariate analyses, the prepubertal increase in ‘∆IGF-ISDS from GH start’ and the ‘GH dose-dependent pubertal ∆IGF-ISDS’ were the most important variables for explaining variation in prepubertal (21 %), pubertal (26 %) and total (28 %) gain in heightSDS.Trial registrationTRN 88–177, not applicable 1988.ConclusionThe dose-dependent change in IGFs was related to a dose-dependent pubertal gain in heightSDS. The attempt to mimic normal physiology by giving a higher GH dose during puberty was associated with both an increase in IGF-I and a dose-dependent gain in heightSDS.Electronic supplementary materialThe online version of this article (doi:10.1186/s12902-015-0080-8) contains supplementary material, which is available to authorized users.

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“…GH stimulates statutory growth directly by its action at the growth plate and indirectly through the production of insulin like growth factor-I (IGF-I) [3]. It also has an effect in most tissues, including lipolysis, protein synthesis, and reduced glucose utilization [4].…”

Section: Introductionmentioning

confidence: 99%

Assessment of Levels of Metabolic Hormones and Lipid Profile in Growth Hormone Deficient Patients

Al-hindawi

Al-Lami

Al-Samarriae

2020

eijs

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Abstract The current study aims to evaluate levels of metabolic hormones and lipid profile in a sample of growth hormone (GH) deficient patients. Seventy five GH deficient patients and twenty healthy subjects used as control group have been participated in this study during their attendance to the National Diabetic Center for Treatment and Research/Al-Mustansiriya University. The studied subjects’ ages were with a range (3-15 years). Blood samples were collected from the studied subjects to determine levels of basal GH, GH2 and GH3 after 1 hr and 1/30 hr provocation with clonidine, respectively; insulin like growth factor (IGF-1); levels of metabolic hormones [thyroid profile: triiodothyronine (T3), thyroxin (T4), and thyroid stimulating hormone (TSH)]; and lipid profile [cholesterol, triglyceride, high density lipoprotein (HDL), low density lipoprotein (LDL) and very low density lipoprotein (VLDL)]. The findings of the anthropometric measurements of the studied groups revealed that a non-significant (P>0.05) difference was found in the weight between the patients and the control, while the mean of height in the patients was significantly (P<0.05) lower than its value in the control. Mean of BMI detected a non-significant (P>0.05) difference between the patients and the control. While mean of BMI percentile and mean of BMI Z-score revealed significant (P<0.05) decrease in the patients compared to their values in the control. The results showed that non-significant (P>0.05) difference was found in level of basal GH between the patients and the control, while a high significant (P<0.01) decrease was found in levels of GH2 and GH3 in the patients group compared to the control group. Level of IGF-1 showed a significant (P<0.05) decrease in the patients compared to the control. The results of metabolic hormones revealed a non-significant (P>0.05) difference in serum T3 between the patients and the control, while a high significant (P<0.01) decrease was found in serum T4 in the patients compared to the control. A non-significant (P>0.05) difference was found in serum TSH between the patients and the control. The data of serum cortisol showed a significant (P<0.05) increase in the patients compared to the control. The results of lipid profile showed a non-significant (P>0.05) difference in serum cholesterol between the patients and the control, while triglyceride showed a significant (P<0.05) increase in the patients compared to the control. A non-significant (P>0.05) difference was found in serum HDL between the patients and the control, while a significant (P<0.05) increase was found in levels of LDL and VLDL in the patients compared to the control. It can be concluded from the present study that diagnosis of GHD cannot be done at the basal serum of GH. A high level of GH was detected after 1 hr. provocation with clonidine compared with its value after 1/30 hr. provocation. The IGF-1 is an appropriate parameter to expect GHD in children and adolescences whom GHD was detected by GH stimulation testing. Low GH secretion is associated with high level of cortisol resulting in GHD. Patients with GHD displayed a tendency towards lipids disturbances.

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Different thresholds of tissue-specific dose-responses to growth hormone in short prepubertal children

Cited by 12 publications

References 44 publications

Combined Treatment With GH and IGF-I: Additive Effect on Cortical Bone Mass But Not on Linear Bone Growth in Female Rats

Combined Treatment With GH and IGF-I: Additive Effect on Cortical Bone Mass But Not on Linear Bone Growth in Female Rats

Growth hormone (GH) dose-dependent IGF-I response relates to pubertal height gain

Assessment of Levels of Metabolic Hormones and Lipid Profile in Growth Hormone Deficient Patients

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