scholarly journals Expression of insulin target genes in skeletal muscle and adipose tissue in adult patients with growth hormone deficiency: effect of one year recombinant human growth hormone therapy

2001 ◽  
Vol 171 (2) ◽  
pp. 285-292 ◽  
Author(s):  
Y Khalfallah ◽  
G Sassolas ◽  
F Borson-Chazot ◽  
N Vega ◽  
H Vidal

Our aim was to investigate the effects of one year recombinant human growth hormone (rhGH) therapy on the regulation by insulin of gene expression in muscle and adipose tissue in adults with secondary GH deficiency (GHD). Six GHD subjects without upper-body obesity were submitted to a 3-h euglycemic hyperinsulinemic clamp before and after one year of rhGH therapy. Muscle and abdominal subcutaneous adipose tissue biopsies were taken before and at the end of each clamp. The mRNA levels of insulin receptor, p85 alpha-phosphatidylinositol-3 kinase (p85 alpha PI-3K), insulin dependent glucose transporter (Glut4), hexokinase II, glycogen synthase, lipoprotein lipase (LPL) in muscle and in adipose tissue, hormone sensitive lipase and peroxisome proliferator-activated receptor gamma (PPAR gamma) in adipose tissue were quantified by RT-competitive PCR. One year treatment with rhGH (1.25 IU/day) increased plasma IGF-I concentrations (54+/-7 vs 154+/-11 ng/ml, P<0.01) but did not affect insulin-stimulated glucose disposal rate measured during the hyperinsulinemic clamp (74+/-9 vs 85+/-5 micromol/kg free fat mass/min). Insulin significantly increased p85 alpha PI-3K, hexokinase II and Glut4 mRNA levels in muscle both before and after rhGH treatment. One year of GH therapy increased LPL mRNA levels in muscle (38+/-2 vs 70+/-7 amol/microg total RNA, P<0.05) and in adipose tissue (2490+/-260 vs 4860+/-880 amol/microg total RNA, P<0.05), but did not change the expression of the other mRNAs. We conclude from this study that GH therapy did not alter whole body insulin sensitivity and the response of gene expression to insulin in skeletal muscle of adult GHD patients, but it did increase LPL expression in muscle and adipose tissue. This result could be related to the documented beneficial effect of GH therapy on lipid metabolism.

2014 ◽  
Vol 4 (1-2) ◽  
pp. 1-13 ◽  
Author(s):  
Hans-Peter Schwarz ◽  
Dorota Birkholz-Walerzak ◽  
Mieczyslaw Szalecki ◽  
Mieczyslaw Walczak ◽  
Corina Galesanu ◽  
...  

Author(s):  
Gajanthan Muthuvel ◽  
Andrew Dauber ◽  
Eirene Alexandrou ◽  
Leah Tyzinski ◽  
Melissa Andrew ◽  
...  

Abstract Context Patients with aggrecan (ACAN) deficiency present with dominantly inherited short stature, often with advanced skeletal maturation and premature growth cessation. There is a paucity of information on the effects of growth-promoting interventions. Objective The aim of this study was to evaluate the efficacy and safety of recombinant human growth hormone (rhGH) therapy on linear growth in children with ACAN deficiency. Design and Setting Open-label, single-arm, prospective study at Cincinnati Children’s Hospital Medical Center. Patients Ten treatment-naïve patients were recruited. Inclusion criteria were: a confirmed heterozygous mutation in ACAN, age ≥ 2 years, pre-pubertal, bone age (BA) ≥ chronological age (CA), and normal IGF-I concentration. Intervention Treatment with rhGH (50 mcg/kg/day) over one year. Main Outcome Measure(s) Main outcomes measured were height velocity (HV) and change in (Δ) height SD (HtSDS). Results Ten patients (six females) were enrolled with median CA of 5.6 yrs (range 2.4 to 9.7). Baseline median HtSDS was -2.5 (range -4.3 to -1.1). Median baseline BA was 6.9 yrs (range 2.5 to 10.0), with median BA/CA of 1.2 (range 0.9 to 1.5). Median pre-treatment HV was 5.2 cm/y (range 3.8 to 7.1), increased to 8.3 cm/y (range 7.3 to 11.2) after one year of therapy (p=0.004). Median ΔHtSDS after one year was +0.62 (range +0.35 to +1.39) (p=0.002). Skeletal maturation did not advance inappropriately (median Δ BA/CA -0.1, p=0.09). No adverse events related to rhGH were observed. Conclusion Treatment with rhGH improved linear growth in a cohort of patients with short stature due to ACAN deficiency.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Jing Wu ◽  
Fei Zhao ◽  
Yuan Zhang ◽  
Jiang Xue ◽  
Jiangying Kuang ◽  
...  

It has been recognized that people with obesity are more likely to have low growth hormone secretion. Recent studies have also confirmed that the abnormalities of the growth hormone/insulin-like growth factor 1 axis were associated with cardiovascular complications in people with obesity. However, little is known about whether recombinant human growth hormone therapy could improve cardiovascular and metabolic risks in obese children. This study aims to evaluate the effect of one-year growth hormone therapy on obesity-related comorbidities and to assess the safety in Chinese boys with obesity. Eighteen boys with obesity were treated with recombinant human growth hormone for one year. Anthropometric measurements, endocrine testing, and cardiovascular risk markers were performed in all obese boys in baseline, and follow-up visits were performed at 3 months, 6 months, 9 months, and one year, respectively. After one year of recombinant human growth hormone treatment, the body mass index standard deviation scores decreased (P<0.001) and insulin-like growth factor 1 levels increased (P<0.001). GH treatment also reduced low density lipoprotein cholesterol (P<0.001), total cholesterol (P<0.001), triglycerides (P=0.042), and alanine aminotransferase (P=0.027) when compared with the baseline. One-year of recombinant human growth hormone treatment could improve cardiometabolic risk markers, without adverse effects on glucose homeostasis in boys with obesity.


Author(s):  
А. Й. Мазуркевич ◽  
В. В. Ковпак ◽  
О. С. Ковпак

Досліджено вплив гормону росту (rhGH) у різних концентраціях та Biolaminin 521 LN на проліферативну активність та генетичну стабільність стовбурових клітин, отриманих з кісткового мозку, жирової тканини та міокарду кота. Встановлено, що гормон росту у низьких концентраціях (10 нг/мл) позитивно впливає на проліферативну активність стовбурових клітин, отриманих із жирової тканини та міокарду кота. Разом із тим, на культуру стовбурових клітин кісткового мозку ефект низьких концентрацій rhGH був протилежний. Культивування стовбурових клітин за додавання Biolaminin 521 LN призвело до достовірного збільшення індексу проліферації у всіх досліджуваних культурах. За даними цитогенетичного аналізу встановлено, що додавання гормону росту у культуральне середовище не призводить до достовірного збільшення кількості генетичних помилок.  Водночас, додавання Biolaminin 521 LN призводить до зменшення кількості клітин із зміненим каріотипом (у порівнянні з контролем) у всіх досліджуваних культурах. The usage of cell technology in clinical practice requires a large amount of cell material. It in turn provokes the development of methods that will allow to obtain a greater amount of cell material for a much shorter period of time. According to literary sources it is known that the growth hormone and the Biolaminin LN 521 can have a positive influence on the mitotic activity of stem cells. Considering the differences in the cell composition of the cell cultures obtained from different tissues, the effects of recombinant human growth hormone (rhGH) and Biolaminin 521 LN will be different. Therefore, our aim was to study the effects of recombinant human growth hormone (rhGH) in various concentrations and to study the Biolaminin LN 521 for the proliferative activity of stem cells obtained from bone marrow, adipose tissue and cardiac muscle of cat. The effects of recombinant human growth hormone (rhGH) in various concentrations and the effects of Biolaminin LN 521 for proliferative activity and genetic stability of stem cells obtained from bone marrow, adipose tissue and cardiac muscle of cat were studied. It was found that the growth hormone has a positive effect on the proliferative activity of stem cells in cell cultures of adipose tissue and cardiac muscle of cat at low concentrations (10 ng/ml), while the effect on the cell culture of bone marrow stem cells was the opposite. According to the cytogenetic analysis it was found that adding recombinant human growth hormone to the culture media does not lead to a significant increase in the number of genetic errors, while adding the Biolaminin 521 LN leads to a decrease in the number of cells with altered karyotype (in comparison with control) in all the studied cell cultures.


2021 ◽  
Vol 10 (21) ◽  
pp. 5100
Author(s):  
Ewelina Witkowska-Sędek ◽  
Anna Małgorzata Kucharska ◽  
Małgorzata Rumińska ◽  
Monika Paluchowska ◽  
Beata Pyrżak

Background: Hypothyroidism in children leads to growth retardation. However, there is some evidence that recombinant human growth hormone (rhGH) therapy could suppress thyroid function. The most common observation in rhGH-treated patients is a decrease in thyroxine levels, which is reported as transient, but the studies in the field are inconsistent. We aimed to evaluate thyroid function in initially euthyroid children with idiopathic isolated GH deficiency during long-term rhGH therapy and to determine who is at a higher risk of thyroid function alterations during the therapy. Methods: The study group consisted of 101 children treated with rhGH for at least three years. Serum TSH and fT4 levels were determined at baseline, after the first six months and after each full year of therapy. The associations between changes in thyroid hormone levels during rhGH therapy and GH deficit, insulin-like growth factor-1 levels and growth response were investigated. Results: A significant decrease in fT4 levels (p = 0.01) was found as early as after the first six months of rhGH therapy. This effect persisted in the subsequent years of treatment without any significant changes in TSH values and tended to be rhGH dose related. Children with a greater fT4 decrease after the initiation of rhGH therapy were older, had higher bone age and responded to that therapy worse than children with lower fT4 changes. Conclusions: Our study revealed a long-term decrease in fT4 levels during rhGH therapy in initially euthyroid GHD children. The decrease in fT4 levels was associated with a lower growth response to rhGH therapy.


2021 ◽  
Vol 10 (22) ◽  
pp. 5354
Author(s):  
Anna Małgorzata Kucharska ◽  
Ewelina Witkowska-Sędek ◽  
Małgorzata Rumińska ◽  
Beata Pyrżak

The alterations in thyroid function during recombinant human growth hormone (rhGH) treatment have been reported by many authors since this therapy became widely available for patients with growth hormone deficiency (GHD). Decrease of thyroxine level is the most frequent observation in patients treated with rhGH. This paper presents literature data describing changes in thyroid function related to rhGH therapy and a current explanation of mechanisms involved in this phenomenon. The effect of GH on the hypothalamic-pituitary-thyroid (HPT) axis is dependent on a multilevel regulation beginning from influence on the central axis, thyroid, and extra-thyroidal deiodinases activity as well as the impact on thyroid hormone receptors on the end. Changes in central and peripheral regulation could overlap during rhGH therapy, resulting in central hypothyroidism or an isolated slight deficiency of thyroxine. The regular monitoring of thyroid function is recommended in patients treated with rhGH and the decision of levothyroxine (L-thyroxine) supplementation should be made in the clinical context, taking into account thyroid hormone levels, as well as the chance for satisfactory growth improvement.


Sign in / Sign up

Export Citation Format

Share Document