Growth Hormone & Igf Research最新文献

Objective

It is well established that growth hormone (GH) has the ability to stimulate lipolysis. The effects of GH on adipocyte differentiation and browning have not been clearly described. Therefore, the present study aimed to elucidate the role of GH in the differentiation and browning of bovine subcutaneous adipocytes as well as its underlying molecular mechanisms.

Methods

We first treated bovine subcutaneous preadipocytes with different concentrations (0, 10, 100, and 500 ng/mL) of GH for 8 days and measured lipid accumulation and gene expression. Afterward, we treated preadipocytes and mature adipocytes with 500 ng/mL GH and determined differentiation and browning-related indicators. Finally, we investigated the expression of STAT5B in both preadipocytes and mature adipocytes after GH treatment.

Results

We demonstrated that GH inhibited lipid accumulation and decreased the expression levels of adipogenic key genes (SCD1, SREBP1, PPARγ, and CEBPα) during adipocyte differentiation. Moreover, we observed that the inhibitory effect of GH on the early stage of adipocyte differentiation (0–2 days) was stronger than that on the later stage of adipocyte differentiation (2–8 days). We also found that GH promoted the expression levels of browning-related genes such as uncoupling protein 1 (UCP1) in mature adipocytes. Concurrently, GH promoted mitochondrial biogenesis and increased the expression levels of mitochondrial biogenesis-related genes. In addition, GH promoted phosphorylation of signal transducers and activator of transcription 5 b (STAT5B) and contributed to translocation of STAT5B to nucleus. After blocking the expression of STAT5B protein, GH weakened the inhibition of adipogenic key genes and reduced the promotion of browning-related genes in bovine subcutaneous adipocytes.

Conclusions

GH can inhibit adipocyte differentiation and promote adipocyte browning by regulating STAT5B in bovine subcutaneous adipocytes.

Objective

Neurosteroids (NSs) are a distinct hormone group and, they are known for their contribution into the status of mood and cognitive functions. Whether they are also involved in the mood disturbances and cognition in acromegaly is not known. Herein we aimed to evaluate the relation of mood status and cognitive functions with the NS levels in cases with acromegaly.

Design

A total of 33 cases with acromegaly composed the acromegaly group (AG) and, 30 age and gender-matched cases without acromegaly composed the control group (CG). The levels of Allopregnanolone (AP), pregnenolone (PRG), 24S-hydroxycholesterol (24OHC), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androsterone (ADT), GH and IGF-1 were measured in each group. Beck Depression Inventory (BDI) was used to assess depressive symptoms, whereas an extensive neuropsychological assessment with several neurocognitive tests were carried out for each subject by an experienced psychologist.

Results

Cases with acromegaly had lower 24OHC and DHEA levels (p = 0.002 and p = 0.007, respectively) in comparison to CG. Of the cognitive functions time to complete 1 s Series was significantly higher and, the scores on Switching Verbal Fluency Test, Boston Naming Test (BNT)-semantic and BNT-phonological, the highest learning point of Oktem Verbal Memory Processes Test (VMPT) were significantly lower in cases with acromegaly in comparison to those in controls (p = 0.004, p = 0.01, p < 0.001, p = 0.02 and p = 0.05, respectively). KAS-perseveration errors were higher in CG (p = 0.03). In AG the levels of AP were negatively correlated with the scores on Months backward Test (MBT), Animal Naming Test, Construction, BNT-spontaneous and positively correlated with BNT-incorrect answers; PRG was positively correlated with VMPT-retention scores, ADT was negatively correlated with MBT and 3 s Series scores, DHEAS was positively correlated with VMPT-the highest learning point whereas it was negatively correlated with MBT scores. Additionally, the scores on BDI were positively correlated with DHEA levels in AG.

Conclusion

Cognitive changes may be encountered in acromegaly and, neurosteroids may contribute to the changes in certain cognitive functions.

Objective/design

Approximately 2.9 million children and adults in the US experience traumatic brain injuries (TBIs) annually, most of which are considered mild. TBI can induce varying consequences on pituitary function, with growth hormone deficiency (GHD) among the more commonly reported conditions. Panels of pediatric and adult endocrinologists, neurologists, physical medicine and rehabilitation specialists, and neuropsychologists convened in February and October 2020 to discuss ongoing challenges and provide strategies for detection and optimal management of patients with mild TBI and GHD.

Results

Difficulties include a low rate of seeking medical attention in the population, suboptimal screening tools, cost and complexity of GHD testing, and a lack of consensus regarding when to test or retest for GHD. Additionally, referrals to endocrinologists from other specialists are uncommon. Recommendations from the panels for managing such patients included multidisciplinary guidelines on the diagnosis and management of post-TBI GHD and additional education on long-term metabolic and probable cognitive benefits of GH replacement therapy.

Conclusion

As patients of all ages with mild TBI may develop GHD and/or other pituitary deficiencies, a multidisciplinary approach to provide education to endocrinologists, neurologists, neurosurgeons, traumatologists, and other providers and guidelines for the early identification and management of persistent mild TBI-related GHD are urgently needed.

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