Growth Hormone & Igf Research最新文献

Objective

To understand the growth of teeth and mandibular and maxillary bones in subjects with isolated growth hormone deficiency (IGHD).

Material and methods

Mesiodistal tooth width of 28 maxillary and mandibular dental models of 14 adult IGHD subjects (9 men) were digitalized and compared to 40 models of 20 normal-statured controls (11 men). The mean SDS of the maxillary and mandibular teeth were compared with height, cephalic perimeter, total anterior facial height, total maxillary and mandibular length, and maxillary and mandibular arches.

Results

All average mesiodistal dimensions in absolute values of the 14 dental pairs were reduced in the IGHD group. Eight of 28 (28.6%) mesiodistal dimensions in IGHD subjects of both sexes had an average SDS below −2, thirteen of them (46.4%) had mean SDS between −1 and − 2, and seven of them (25.0%) had SDS above −1. The highest SDS values were the upper lateral incisor (−0.32 in women), and the upper canine (−0.91 in men). The lowest SDS values were the 2nd upper molar (−3.51 in men), and the 2nd upper premolar (−2.64 in women). The ascending order of the mean SDS was height, total maxillary length, total mandibular length, total anterior height of the face, cephalic perimeter, the maxillary arches width, the mesiodistal width of the mandibular teeth, the mesiodistal width of the maxillary teeth and the mandibular arches width.

Conclusions

Reduction in mesiodistal width is present in untreated IGHD adults with magnitude of tooth size reduction being lower than height, cephalic perimeter, total anterior facial height, and most jaw measurements. IGHD abolishes the sexual dimorphism in mesiodistal dental measures.

Objective

To explore whether the reduction of IGF-1 in missed abortion down-regulates PI3K/AKT signaling pathway, thereby causing trophoblast cell apoptosis and reducing the secretion of β-hCG and progesterone.

Design

12 pairs of serum and villous tissues were selected from missed abortion patients and normal early pregnant women who had terminated pregnancy by artificial abortion. The subjects in two groups had same age and gestational week. Wes Simple Western system and qRT-PCR were used to detect the expression of IGF-1, IGF-1R, PI3K/AKT signaling pathway and apoptosis-related factors in villous tissues. Radioimmunoassay and Enzyme-linked immunosorbent assay were used to detect β-hCG, progesterone and IGF-1 in serum.

Results

The serum levels of β-hCG, progesterone and IGF-1 were decreased in missed abortion group than those in normal early pregnant women. In addition, compared with normal early pregnant women, the genes and proteins levels of IGF-1 and PI3K/AKT signaling pathway and anti-apoptosis related factors were significantly decreased.

Conclusions

Our results suggested that the reduction of IGF-1 in missed abortion patients could down-regulate the expression of PI3K/AKT signaling pathway, thereby increasing the apoptosis of trophoblast cells, leading to decreased secretion of β-hCG and progesterone, which may be one of the important mechanisms of missed abortion.

Purpose

Attention-deficit/hyperactivity disorder (ADHD) is typically a chronic, often lifelong condition. Data suggest that ADHD itself and its treatment may be associated with dysregulated growth, including height and BMI. The reason for this association is yet unknown. The objective of this study was to examine differences in growth hormone (GH) response to exercise between children who had received a diagnosis of ADHD and age- and gender-matched controls. We reasoned that the normal increase in circulating GH seen in response to exercise would be blunted in children with ADHD.

Methods

We recruited 13 treatment-naïve children with newly diagnosed ADHD and 14 age-matched controls (all male) and measured GH response to an exercise test in which the work was scaled to each subject's physical capability.

Results

There was no difference in the peak heart rate achieved during exercise between controls and ADHD participants (196.6 ± 1.5 vs. 196.5 ± 2.1 bpm, respectively) and lactate response to exercise (53.8 ± 5.0 vs. 47.9 ± 3.8 mg/dl, respectively). After exercise, GH increased significantly in the control subjects (p < 0.005), while GH responses were substantially blunted in the ADHD group (p = NS) even though the work performed did not differ from controls.

Conclusions

Our data suggest that GH excretion after exercise challenge in children with ADHD is impaired. This can be detected using a minimally invasive, nonpharmacologic challenge and may link ADHD with growth impairment in some children.

Trial registration number: NCT00945971

Objective

We examined whether auto/paracrine insulin-like growth factor-1 (IGF-1) contributes to the phosphorylation of Akt and ERK in chicken myotubes.

Methods

Chicken myotubes were treated with IGF-1 siRNA, and then total RNA and protein were harvested for real-time PCR and western blot analysis.

Results

Treatment with IGF-1 siRNA inhibited the phosphorylation of Akt and ERK, but not of ribosomal protein S6, in chicken myotubes. Interestingly, IGF-1 siRNA downregulated the expression of IGF-2.

Conclusions

The results of this study suggest that auto/paracrine IGF-1 contributes to Akt and ERK phosphorylation in chicken myotubes.

Background

Despite many similarities between the structure, receptors, proliferative and growth promoting actions, the relationship between Prolactin (PRL) and Growth Hormone (GH) in clinical conditions has received little attention.

Objective

To determine the PRL response to GH stimulation tests.

Subjects

Prepubertal and early pubertal boys (n = 581) and girls (n = 502) with idiopathic, non-syndromatic short stature.

Design

Data was retrieved from the computerized records of the Endocrine Laboratory, Schneider Children's Medical Center. Peak GH and PRL levels during GH stimulation tests with glucagon (Gluc), Clonidine (Clon) and Clonidine with arginine (Clon+Arg), were compared. Both PRL and GH were determined by radioimmunoassay.

Results

Whereas Gluc stimulated both GH and PRL to similar levels, Clon alone or combined with Arg suppressed the PRL secretion (p < 0.0001). It is also evident that in both boys and girls Clon alone and Clon±Arg are superior to Gluc in GH stimulation. The higher GH levels during Clon+Arg than with Clon alone are attributed to the pubertal stage.

Conclusion

This study provides further information on the Prolactin-Growth hormone relationship in children.

Objective

The GH and IGF-1 axis is a candidate disease-modifying target in nonalcoholic fatty liver disease (NAFLD) given its lipolytic, anti-inflammatory and anti-fibrotic properties. IGF-1 receptor (IGF-1R) and GH receptor (GHR) expression in adult, human hepatic tissue is not well understood across the spectrum of NAFLD severity. Therefore, we sought to investigate hepatic IGF-1R and GHR expression in subjects with NAFLD utilizing gene expression analysis (GEA) and immunohistochemistry (IHC).

Design

GEA (n = 318) and IHC (n = 30) cohorts were identified from the Massachusetts General Hospital NAFLD Tissue Repository. GEA subjects were categorized based on histopathology as normal liver histology (NLH), steatosis only (Steatosis), nonalcoholic steatohepatitis (NASH) without fibrosis (NASH F0), and NASH with fibrosis (NASH F1–4) with GEA by the Nanostring nCounter assay. IHC subjects were matched for age, body mass index (BMI), sex, and diabetic status across three groups (n = 10 each): NLH, Steatosis, and NASH with fibrosis (NASH F1–3). IHC for IGF-1R, IGF-1 and GHR was performed on formalin-fixed, paraffin-embedded hepatic tissue samples.

Results

IGF-1R gene expression did not differ across NAFLD severity while IGF-1 gene expression decreased with increasing NAFLD severity, including when controlled for BMI and age. GHR expression did not differ by severity of NAFLD based on GEA or IHC.

Conclusions

IGF-1R and GHR expression levels were not significantly different across NAFLD disease severity. However, expression of IGF-1 was lower with increasing severity of NAFLD. Additional research is needed regarding the contribution of the GH/IGF-1 axis to the pathophysiology of NAFLD and NASH.

Objective

Chagas disease (CD) is caused by the protozoan parasite, Trypanosoma cruzi. It affects 7 to 8 million people worldwide and leads to approximately 50,000 deaths per year. In vitro and in vivo studies had demonstrated that Trypanosoma cruziinfection causes an imbalance in the hypothalamic-pituitary-adrenal (HPA) axis that is accompanied by a progressive decrease in growth hormone (GH) and prolactin (PRL) production. In humans, inactivating mutations in the GH receptor gene cause Laron Syndrome (LS), an autosomal recessive disorder. Affected subjects are short, have increased adiposity, decreased insulin-like growth factor-I (IGFI), increased serum GH levels, are highly resistant to diabetes and cancer, and display slow cognitive decline. In addition, CD incidence in these individuals is diminished despite living in highly endemic areas. Consequently, we decided to investigate the in vitro effect of GH/IGF-I on T. cruzi infection.

Design

We first treated the parasite and/or host cells with different peptide hormones including GH, IGFI, and PRL. Then, we treated cells using different combinations of GH/IGF-I attempting to mimic the GH/IGF-I serum levels observed in LS subjects.

Results

We found that exogenous GH confers protection against T. cruzi infection. Moreover, this effect is mediated by GH and not IGFI. The combination of relatively high GH (50 ng/ml) and low IGF-I (20 ng/ml), mimicking the hormonal pattern seen in LS individuals, consistently decreased T. cruzi infection in vitro.

Conclusions

The combination of relatively high GH and low IGF-I serum levels in LS individuals may be an underlying condition providing partial protection against T. cruzi infection.

Objective

Decathlon is a combined track and field competition, consisting of ten, mainly anaerobic events. Insulin-like growth factor-I (IGF1) axis plays a pivotal role in athletes' structural and functional muscle adaptation to exercise training, and in their competitive performance. Based on the great demand for speed physiological characteristics among decathlon athletes, the aim of this study was to assess the prevalence of IGF genetic polymorphisms among decathletes, to present an optimal genetic profile for enhancing performance.

Methods

The participants included 151 male athletes and 75 male non-athletic controls from Israel and Estonia. Athletes were divided into four groups, according to the field of expertise: (a) 40 sprinters and long jumpers; (b) 40 middle distance runners; (c) 44 Weightlifters; and (d) 27 decathletes. Genomic DNA was extracted from the participants' buccal epithelial cells using standard protocol and then analyzed for IGF1 axis related genetic polymorphism using the allelic discrimination assay.

Results

A significantly higher prevalence of the IGF1 rs35767 TT genotype was found among decathletes compared to the other athletes, as well as a lower prevalence of the IGF1 rs7136446 GG genotype, a higher prevalence of the IGF1R rs1464430 AA genotype, and a higher prevalence of the IGF2 rs680 GG genotype. Moreover, among the decathletes, carriers of the IGF1 rs7136446 GG genotype achieved higher decathlon scores compared to A-allele carriers.

Conclusions

The findings of this study suggest a potential beneficial role for some IGF-axis polymorphisms (mainly the IGF1 1245 TT and the IGF2 GG) among decathletes, both of which are associated with improved speed performance.

Objective

Anorexia nervosa (AN) is a severe mental disorder that is characterized by restriction of energy intake, low weight, and endocrine abnormalities. One of the known endocrine changes in relation to underweight is in the GH/IGF-I axis. The aim of the study was (a) to investigate longitudinal characteristics of the IGF-I-change during therapy and weight gain in adult AN, (b) to determine relationships between IGF-I and leptin, (c) to characterize patients with weak and pronounced hormonal reactions to underweight.

Design

Data was assessed from 19 AN patients. Over the first two months, serum IGF-I concentrations were assessed on a weekly basis; thereafter on a monthly basis. The trend of IGF-I values over time was analyzed using individual growth models.

Results

In total, n = 177 IGF-I measurements were analyzed. IGF-I increased significantly dependent on BMI (slope = 20.81, p < 0.001), not modulated by duration of disease. The increase in IGF-I was significantly related to the increase in leptin concentrations over time (slope = 15.57, p < 0.001). Patients with a weaker hormonal reaction to underweight were significantly older compared to patients with a pronounced hormonal reaction (t(17) = 3.07, p = 0.007).

Conclusions

During treatment, IGF-I change is clearly related to BMI as well as to leptin. Age appears to be associated with the IGF-I response to underweight.

The most frequent diagnosis underlying the finding of an elevated growth hormone (GH) and insulin-like growth factor-1 (IGF-1) is acromegaly due to a GH-secreting pituitary tumour. However, GH and IGF-1 levels can be discordant in patients with acromegaly due to early or partially treated disease, or there might be another cause of high GH or high IGF-1 unrelated to acromegaly, such as pre-analytical and technical pitfalls, physiological circumstances and pathological conditions. High GH and normal or low serum IGF-1, or alternatively, normal GH with elevated serum IGF-1, should be carefully assessed to avoid misinterpreting the activity of acromegaly or misdiagnosing a patient with acromegaly. We summarise here these biochemical discrepancies in the evaluation of the somatotroph axis.