Growth Hormone & Igf Research最新文献

Objectives

Insulin-like growth factor 1 receptor (IGF-1R) is a transmembrane tyrosine kinase receptor of the insulin receptor family. Its expression is consistently increased in hepatocellular carcinoma (HCC) tissue, and it participates in hepatic carcinogenesis. Targeting IGF-1R may be a potential therapeutic approach against hepatocellular carcinoma. This study therefore aimed to explore the effect of IGF-1R on hepatocellular carcinoma cells.

Methods

IGF-1R silencing cell lines were established by small-interfering RNAs in hepatocellular carcinoma cell line SMMC7721, after which the proliferation, invasion, and apoptosis of SMMC7721 was evaluated. The activation of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and the expression of bone morphogenetic protein (BMP)-2 and BMP-7 were measured using Western blot analysis.

Results

The results indicated that the knockdown of IGF-1R can inhibit the proliferation and invasion of HCC and promote the apoptosis of SMMC7721 by inhibiting the PI3K/AKT signaling pathway. Furthermore, depletion of IGF-1R was found to suppress the expression of BMP-2 and BMP-7.

Conclusions

The findings suggest that IGF-1R plays an important role in the progression of HCC. Therefore, IGF-1R is a potential target for the treatment of HCC in clinic.

Long-acting growth hormone (LAGH) is emerging to be a new preparation for treatment of short stature. We aimed to determine whether 12-month treatment with LAGH in patients with idiopathic short stature has an effect on the nocturnal endogenous growth hormone (GH) secretion and metabolic consequences and efficacy. Participants included 10 GH-naïve prepubertal children with idiopathic short stature (ISS). One patient was withdrawn due to own decline during study. Participants were randomized on a 1:1 ratio to receive either a daily GH (0.37 mg/kg/week) or once-weekly LAGH (0.7 mg/kg/week) over a 12-month period. Nocturnal endogenous GH secretory profiles obtained from 12-h blood samplings at 30-min interval were assessed at baseline and 2 weeks after the completion of GH treatment. Post-treatment changes in height velocity, height standard deviation score (SDS), metabolic parameters, and adverse events were measured. A total of 4 patients received LAGH, and 5 patients received daily GH. Nocturnal endogenous GH secretory profiles, such as mean serum GH concentrations, frequency, amplitude, interpulse interval of spontaneous GH secretory bursts, and mass of GH released per secretory burst were similar at baseline and after 12-month treatment in both groups. The efficacy and safety after LAGH treatment for 12 months were similar to those of daily GH. In conclusions, these findings indicated that LAGH does not suppress endogenous GH secretion, and can be used for treatment of non-GH deficient short stature with similar efficacy and safety compared to daily GH. These may contribute to define and develop treatment and follow-up protocols for LAGH use in ISS patients.

Purpose

To evaluate the role of metformin on thyroid cancer risk in patients with acromegaly.

Methods

Medical charts of 534 patients with acromegaly that were followed-up between 1983 and 2019 were reviewed. Patients with follow-up duration at least 6 months were included. Cohort entry was defined as first visit date. The date of each case's thyroid cancer diagnosis was defined as index date. Patients were followed until the index date, death, or last visit date, whichever came first. Nested case-control study design was selected to evaluate the association between metformin and the thyroid cancer risk in patients with acromegaly.

Results

291 patients with acromegaly were included into final analysis. The mean age at acromegaly diagnosis was 42.3 ± 1.3 years. The median follow-up duration was 76 [34–132] months. Among 291 patients, 13 patients (4.5%) had thyroid cancer. Thirty-one percent (n = 92) of the patients used metformin for 6 months or longer. One standard deviation (SD) increase in average growth hormone increased the odds of having thyroid cancer by 1.164 folds (p = 0.017). One SD increase of the average insulin-like growth factor 1 to upper limit of normal ratio increased the odds of having thyroid cancer by 1.201 folds (p = 0.004). If a patient used metformin for at least 6 months, the odds to have thyroid cancer was decreased, multiplied by 0.62 with a 95% confidence interval of [0.47, 0.83] (p = 0.0013). The risk of thyroid cancer decreased with increasing duration of metformin use.

Conclusion

Metformin may decrease the thyroid cancer risk in patients with acromegaly.

Objective

Acromegaly is a disorder caused by hypersecretion of growth hormone (GH), resulting in excessive levels of insulin-like growth factor 1 (IGF-1), and almost always due to a pituitary tumor. It is classically associated with acral enlargement, prominent facial features and soft tissue overgrowth. Skin manifestations include hirsutism, acne, skin tags, oily skin and acanthosis nigricans. However, other uncommon dermatological features, such as cutis verticis gyrata (CVG), may also occur. Here, we review acromegaly-related CVG aiming to raise awareness for its possible occurrence in this setting, and we discuss its pathophysiology, presentation, management and differential diagnosis.

Design

A comprehensive literature search regarding CVG, particularly CVG related to acromegaly, has been carried out. Case reports, original studies and review papers, were considered.

Results

CVG is a rare benign skin lesion characterized by thickened and folded scalp, resembling the brain gyri and sulci. The diagnosis of CVG mainly relies on clinical examination, although tissue biopsy may be necessary in case of uncertain etiology. In acromegaly, CVG appears to be driven by the trophic effects of GH and IGF-1 on skin and soft tissues. While CVG is uncommon in acromegaly, it seems to occur more frequently in male patients. The management of acromegaly-related CVG essentially relies on controlling the serum levels of GH and IGF-1. Surgical skin procedures should be reserved for patients with severe aesthetic distress, after achieving the best possible control of acromegaly.

Conclusions

CVG is a rare manifestation of acromegaly that may allow an earlier diagnosis and a swifter treatment of these patients, which in turn may improve or entirely reverse such remarkable skin lesions.

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.