Growth Hormone & Igf Research最新文献

Objective

Phoenixin-20 (Pnx-20) is a bioactive peptide with endocrine-like actions in vertebrates. Recent studies suggest Pnx-20 promotes growth hormone/insulin-like growth factors (Gh/Igf) axis, an important endocrine regulator of growth in mammals and fish.

Design

In this research, we determined whether Pnx-20 affects the different members of the Igf family, its binding proteins and receptors (Igf-system) in zebrafish liver and muscle.

Results

In vivo administration of Pnx-20 downregulated igfs, igf receptors (igfrs) and igf binding protein (igfbp) 5 mRNA expression in the liver of male and female zebrafish at both 1 and 6 h post-intraperitoneal (IP) injection. Interestingly, this effect occurred at a relatively earlier timepoint in female zebrafish suggesting sex-specific differences in Pnx-20 action. Besides, either 6 or 24 h in vitro incubations with Pnx-20 downregulated the expression of all igfs, igfrs and igfbp5 mRNAs (except igf2a) analyzed in a zebrafish liver cell (ZFL) line. Moreover, siRNA-mediated knockdown of Pnx-20 upregulated all Igf-system mRNAs analyzed in ZFL cells. Together, these results (both in vivo and in vitro) revealed a general suppressive action for both endogenous and exogenous Pnx-20 on the hepatic Igf-system of zebrafish. In contrast, a general sex-specific upregulation of the Igf-system mRNAs analyzed was found in the muscle of Pnx-20 injected fish. Future research should explore the sex- and time-differences observed in the present study.

Conclusions

Collectively, this research shows that Pnx-20 is a tissue-specific regulator of the liver (suppressor) and muscle (stimulant) Igf signaling in both male and female zebrafish.

Objective

Hyperoxic gas inhalation during exercise may negatively affect all-out sprint interval exercise (SIE)-induced hormonal, metabolic, and angiogenic responses. We investigated the effects of acute all-out SIE under systemic hyperoxia on hormonal, metabolic, and angiogenic responses.

Design

This was a randomised-crossover trial. Ten healthy males (mean ± standard error of age = 23.1 ± 0.9 years; height = 171.0 ± 1.6 cm; body mass = 66.2 ± 2.0 kg; body mass index = 22.6 ± 0.5 kg/m²) completed the following two experimental regimens: 1) SIE under normoxia and 2) SIE under systemic hyperoxia (FiO₂ = 60%). The subjects performed four bouts of 30-s maximal cycling efforts with 4 min recovery between efforts. The circulating levels of hormonal (growth hormone, epinephrine, and norepinephrine), metabolic (glucose, free fatty acid, and lactate), and angiogenic (vascular endothelial growth factor, matrix metalloproteinase-2 and -9, and endostatin) markers were measured before and at 0 (immediately after the regimen), 30, and 120 min after both regimens.

Results

In response to both SIE regimens, the peak and mean power outputs gradually decreased over the intermittent exercise session compared with those in the first bout (p < 0.01) with no significant differences between the regimens. Both regimens significantly increased the circulating concentrations of all hormonal, metabolic, and angiogenic markers (p < 0.01). However, there were no significant differences in the levels of these markers in response to the two regimens at any time point (p > 0.05).

Conclusion

These findings suggest that acute systemic hyperoxia does not influence the hormonal, metabolic, and angiogenic responses to all-out SIE.

Patients with growth hormone deficiency (GHD) have many clinical features in common with Cushing's syndrome (glucocorticoid excess) – notably visceral obesity, insulin resistance, muscle myopathy and increased vascular mortality. Within key metabolic tissues, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts cortisone to the active glucocorticoid, cortisol (11-dehydrocorticosterone and corticosterone in rodents respectively), and thus amplifies local glucocorticoid action.

We hypothesize that 11β-HSD1 expression is negatively regulated by growth hormone (GH), and that GHD patients have elevated 11β-HSD1 within key metabolic tissues (leading to increased intracellular cortisol generation) which contributes to the clinical features of this disease.

To identify the impact of GH excess/resistance on 11β-HSD1 in vivo, we measured mRNA expression in key metabolic tissues of giant mice expressing the bovine GH (bGH) gene, dwarf mice with a disrupted GH receptor (GHRKO) gene and mice expressing a gene encoding a GH receptor antagonist (GHA). Additionally, we assessed urine steroid markers of 11β-HSD1 activity in both GHRKO and bGH animals.

11β-HSD1 expression was decreased in gastrocnemius muscle (0.43-fold, p < 0.05), subcutaneous adipose (0.53-fold, p < 0.05) and epididymal adipose tissue (0.40-fold, p < 0.05), but not liver, in bGH mice compared to WT controls. This was paralleled by an increased percentage of 11-DHC (inactive glucocorticoid) present in the urine of bGH mice compared to WT controls (2.5-fold, p < 0.01) - consistent with decreased systemic 11β-HSD1 activity. By contrast, expression of 11β-HSD1 was increased in the liver of GHRKO (2.7-fold, p < 0.05) and GHA mice (2.0-fold, p < 0.05) compared to WT controls, but not gastrocnemius muscle, subcutaneous adipose tissue or epididymal adipose tissue.

In summary, we have demonstrated a negative relationship between GH action and 11β-HSD1 expression which appears to be tissue specific. These data provide evidence that increased intracellular cortisol production within key tissues may contribute to metabolic disease in GHD patients.

Objective

The signaling axis consisting of GH-IGF1-IGFBP3 is the primary signal taht acts prepubertally to influence height development. Growth plate thinning and even premature closure have been reported in children with tumors treated with retinoid chemotherapy, resulting in long bone dysplasia. Growth failure may occur despite received GH treatment, but the reason is unknown. This study investigate the effect of high-dose all-trans retinoic acid (ATRA) on the development of long bones in growing SD rats.

Methods

A total of 20 three-week-old male SD rats were randomly divided into a control group and an experimental group (n = 10). Rats were treated by gavage with or without high-dose ATRA for 10 days. The body weights of the rats were recorded daily. At the end of the experiment, we measured the length of nose-tail and tibia, stained the tibia and liver for pathological tissue and RT-PCR reaction, and measured the levels of serum GH, IGF1 and IGFBP3, and so on.

Results

Compared with controls, experimental rats exhibited reduced body weight and shortened nasal-tail and radial tibial length. Cyp26b1 enzyme activity in the liver was elevated, and histopathological staining revealed that the cartilaginous epiphyseal plate was narrowed, the medullary cavity of trabecular bone was sparse, the number of trabecular bones was decreased, trabecular separation was increased, bone marrow mineralization was enhanced, osteoclastic activity was increased, and circulating GH-IGF1-IGFBP3 levels were decreased. However, RT-PCR reaction results of localized proximal tibiae showed upregulation of IGF1 and downregulation of IGFBP3.

Conclusions

High-dose ATRA intake over a short period of time can reduce GH-IGF1-IGFBP3 levels, affect cartilage and bone homeostasis, and inhibit bone growth in developing animals.

Objectives

The growth of the dental arches depends on GH and insulin-like growth factor type 1 (IGF1), but the consequences of GH deficiency (GHD) on their growth are still unclear, probably due to the acquired etiology of GHD in most described series, often associated with additional pituitary deficits (thyrotrophic, corticotrophic and gonadotrophic hormones), and imperfections of related replacement therapies, which may affect the dental arch growth. To avoid these limitations, we took advantage of a unique cohort of subjects with isolated GH deficiency (IGHD) due the same mutation in the GH releasing hormone receptor gene, living with very low serum GH and low to undetectable circulating IGF1 levels. Our purpose was to analyze the dimensions of maxillary and mandibular dental arches.

Methods

22 adult IGHD (15 untreated and 7 previously partially treated with GH) and 33 controls were enrolled in a cross-sectional study using the Ortho Insight 3D and MeshMixer software,

Results

In untreated IGHD subjects all maxillary arch measures were smaller than controls, while among mandibular arches, only the mandibular canine width and the mandibular arch length were reduced. In partially GH treated subjects only the palate depth, the maxillary canine width, the maxillary and mandibular arch lengths remained smaller than controls.

Conclusions

IGHD reduces the growth of maxillary arch to a greater degree than the mandibular arch, suggesting different control of superior and inferior dental arches. GH treatment increases some of these measures.

Objective

To identify and characterize a novel deletion at the LHX4 gene locus in a proband with growth hormone deficiency (GHD).

Methods

Long range polymerase chain reaction (PCR) amplification was used to confirm the suspected deletion and to identify the rough locations of the end points. Sanger sequencing was carried out to identify the exact end points of the deletion.

Results

Suspected deletion was confirmed via long range PCR amplification. Sanger sequencing identified the end points of the deletion within three nucleotide repeat sequences (“CTT”). The total length of the deleted segment was 12 127 base pairs and it includes complete exon 5 and exon 6 of the LHX4 gene. Therefore the homeodomain motif coded by exons 4 and 5, might be affected.

Conclusion

We have identified a novel deletion that spans exon 5 and exon 6 of the LHX4 gene that could have occurred via microhomology mediated non-recurrent rearrangement. The deletion characterized does not appear to have been reported before. To our knowledge this novel deletion is the first identified LHX4 variant from Sri Lanka and it explains the phenotype of the proband characterized by growth hormone deficiency, hypoplastic anterior pituitary and subsequent deficiency of thyroid stimulating hormone and adrenocorticotropic hormone (ACTH).

Objective

An intrauterine device (IUD) is one of the most effective reversible contraceptive methods currently available. Women who use IUDs may become pregnant, albeit rarely, and many such women continue to use IUDs. Because it is difficult to remove or it may cause miscarriage. This study measured the changes in human leucocyte antigen-G (HLA-G) and insulin-like growth factor II (IGF-II) levels in the decidua and villi to explore the effect of a copper IUD on embryonic development.

Design

A total of 54 samples of decidual and villus tissue were collected from pregnant women with IUDs (27 samples) or without IUDs (27 samples). Hematoxylin-eosin staining was used to identify morphological characteristics. Immunohistochemistry was used to detect HLA-G and IGF-II; the protein expression levels were measured via Western blotting.

Results

HLA-G was expressed on the membranes of trophoblasts of villus tissues and the glandular epithelium, and in stromal cells of decidual tissues, in both the IUD and control groups. IGF-II was expressed in the glandular epithelium and cytoplasm of trophoblasts and decidual cells in both groups. Compared to the control group, IGF-II expression was significantly reduced in villus tissues of the IUD group (p < 0.05). The mean sac diameter was significantly positively correlated with IGF-II expression in the villi (p < 0.05).

Conclusions

A copper IUD may affect embryonic development by regulating the expression of villus IGF-II.

Objective

Cardiovascular (CV) disease is still a major cause of excessive morbidity and mortality in patients with active acromegaly, which may be attributed to a high prevalence of associated pro-atherosclerotic risk factors. However, a direct effect of GH/IGF-1 excess on the vasculature has been previously suggested, warranting further investigation. The present study was designed to investigate whether chronic GH/IGF-1 excess is associated with an increased prevalence of subclinical atherosclerosis in patients with acromegaly.

Design

We measured carotid intima-media thickness (cIMT) and assessed carotid plaques by ultrasonography along with classical CV risk factors in 54 acromegaly patients (34 females, 50 ± 12 years and compared those with 62 (42 females, 53 ± 13 years) age-, sex- and CV risk factors- matched controls. In order to compare cIMT measurements between patients and controls we analyzed common carotid artery far wall data as well as a combined measurement result, which consisted of the mean value of the six different measurements, three at each side.

Results

mean ± SD serum GH and IGF-1 levels were 2.76 ± 4.65 ng/mL and 1.7 ± 1.25 x ULN, respectively, in all acromegaly patients. Age, body mass index, blood pressure, lipid levels, fasting glucose and Framingham's global cardiovascular risk score classification were similar comparing patients and controls. Combined median [IQR] cIMT measurements were similar in acromegaly patients and matched controls (0.59 [0.52–0.66] mm vs. 0.59 [0.52–0.69] mm; P = 0.872) as well as in acromegaly patients with active and controlled disease (0.59 [0.51–0.68] mm vs. 0.60 [0.54–0.68] mm; P = 0.385). No significant correlations were observed between cIMT measurements and GH (Spearman r = 0.1, P = 0.49) or IGF-1 (Spearman r = 0.13, P = 0.37) levels in patients with acromegaly. Carotid atherosclerotic plaques prevalence was similar in patients and controls (26% vs. 32%; P = 0.54) as well as in patients with active and controlled acromegaly (22% vs. 30%; P = 0.537).

Conclusions

Our data suggest that GH/IGF-1 excess itself is not one of the main drivers of subclinical morphological atherosclerosis changes in patients with acromegaly and that optimal control of acromegaly-associated CV risk factors may preserve vasculature structure even when strict biochemical control is not achieved.

Objectives

Pituitary diseases may cause psychiatric and personality alterations. We aimed to compare the personality traits of acromegalic patients with those of patients with non-functioning pituitary adenomas and a healthy control group.

Design

Fifty-eight acromegalic patients, 45 patients with non-functioning adenoma, and 40 healthy subjects were enrolled in the study. Cloninger's Temperament and Character Inventory (TCI), Beck Depression Inventory, Beck Anxiety Inventory, and Rosenberg Self-Esteem Scale (RSES) were used to assess personality, depression, anxiety, and self-esteem.

Results

Depression score was higher in acromegaly and non-functioning adenoma groups than healthy controls. RSES scores were similar among the three groups. Regarding the scales of TCI, only novelty-seeking was significantly reduced in acromegaly and non-functioning adenoma than the control group. Pairwise comparisons revealed that the difference was due to the difference between acromegalic patients and controls. Scales of TCI were correlated with depression and anxiety in patients with acromegaly and non-functioning adenoma but not in healthy controls.

Conclusion

This study showed that novelty-seeking was reduced in patients with acromegaly. Both the hormonal lack and excess and structural changes can lead to cognitive and personality changes in acromegaly. More studies are needed to be carried out about personality characteristics in pituitary diseases.

Purpose

To investigate anterior segment parameters (ASPs) and dry eye disease (DED), including the status of the meibomian glands, in patients with acromegaly.

Methods

In this cross-sectional, comparative study, 36 acromegaly patients and 40 healthy sex- and age-matched controls were included. Participants received a comprehensive ophthalmological examination, including intraocular pressure measurements with Goldmann applanation tonometry (IOP_GAT) and central corneal thickness corrected intraocular pressure (IOP_CCT) measurements, and were evaluated for ASPs and DED. For ASPs, white-to-white (WTW), apical (ACT) and thinnest corneal thickness (TCT), corneal volume (CV), keratometry readings (K₁, K₂, and K_mean), anterior chamber depth (ACD) and volume (ACV), and iridocorneal angle (ICA) were obtained via Sirius topography. DED was assessed with Schirmer's test, tear breakup time (TBUT), and Ocular Surface Disease Index (OSDI) scores. Meibography scores (MSs) were obtained with the Sirius topography device.

Results

Patients had higher mean IOP_GAT (P = .006), IOP_CCT (P = .01), ACT (P = .024), and TCT (P = .005) but narrower ICA (P = .014) than controls. Although Schirmer's test did not differ between the groups (P = .442), patients had higher OSDI (P < .001), higher MS (P = .001), and shorter TBUT (P = .002).

Conclusion

Patients with acromegaly have greater IOP, greater corneal thickness, but narrower ICA than healthy individuals, as well as DED with increased MSs, which suggests meibomian gland dysfunction.