Hormone Insulin-like Growth factor-I Research Articles

Modification of Carp (Osphronemus Gouramy) Growth with Insulin-Like Growth Factor-I Recombinant Mouse in Vivo

Osphronemus gouramy consumption is increasing every year, which causes a high number of inquiries for this fish, which cannot be offset sufficiently by the amount of production. The growth rate of O. gouramy is relatively slow, so achieving the required consumption is relatively long. Quality improvement of productivity by improving the ability of cell metabolism to intake fish feed through hormone injection recombinant mouse insulin-like growth factor-I (IGF-I) is expected to spur growth so that fish production can be increased. This study aims to determine the effect of the hormone IGF-I recombinant mouse on the increased growth of O. gouramy. The benefits of this research are expected to deliver the benefits of science in the form of scientific information to the public in general and fish farmers, especially about the effect of the hormone recombinant mouse IGF-I on the growth of O. gouramy. The research method is carried out experimentally by using a completely randomized design (RAL); this study uses 80 O. gouramy was divided into 4 treatments P0: without hormone injections of IGF-I, P1: injected with the hormone IGF-I at a dose of 10 ng/ml, P2: injected with the hormone IGF-I at a dose of 20 ng/ml and P3: injected with the hormone at a dose of 40 ng/ml each of 5 replicates each test 4 tail O. gouramy. The hormone IGF-I recombinant mouse is done by injection. The treatment with hormone injection of recombinant mouse IGF-I. The parameters measured were growth. The results showed that the treatment hormone injection of recombinant mouse IGF-I with different doses gave significant differences (p <0.05); weight growth (P0: 0 ng/ml = 7,23 gram ± 0,37-gram dan P3: 40 ng/ml = 26,35 gram ± 1,89 gram.); length growth (P0 : 0 ng/ml = 5,76 cm ± 0,38 cm dan P3: 40 ng/ml = 7,93 cm ± 0,07 cm). The conclusion is that recombinant mouse IGF-I increased the growth by increasing in weight and length of O. gouramy, and improvement of the growth occurred in the treatment injection of the dose: 40 ng/ml.

Transgenerational effects of microplastics on Nrf2 signaling, GH/IGF, and HPI axis in marine medaka Oryzias melastigma under different salinities

Little information is available on the toxicity of microplastics (MPs) under different salinities in aquatic organisms. Consequently, the effects of larvae exposure to 180 μg/L MPs with 5.0 μm diameter on growth, antioxidant capacity and stress response were investigated in exposed F1 larvae and unexposed F2 larvae in marine medaka Oryzias melastigma at 5 ‰ and 25 ‰ salinities. Poor growth performance of F1 and F2 larvae and F1 adult fish was merely found under high salinity, as well as changes in the growth hormone/insulin-like growth factor-I (GH/IGF). Although malondialdehyde (MDA) content and antioxidant capacity remained constant in F1 larvae under high salinity, MPs increased MDA content and reduced antioxidant capacity in F2 larvae. Contrarily, MDA and antioxidant capacity increased in F1 and F2 larvae under low salinity. The mRNA expression levels of genes in the NF-E2-related factor 2 (Nrf2) pathway were dysregulated. Cortisol levels in the whole body increased in F1 larvae and recovered to the control level under low salinity while cortisol levels declined in F1 larvae and increased in F2 larvae under high salinity, which was related to the transcriptional regulation of the hypothalamus–pituitary–interrenal (HPI) axis genes. To summary, the present study determined the toxic effects of MPs on growth, antioxidant capacity, and stress response by disturbing Nrf2, HPI, and GH/IGF signaling in exposed larvae and unexposed offspring of marine medaka in a salinity-dependent manner. For the first time, our results highlight the interference effects of salinity on MPs toxicity in fish.

Combined effects of crowding stress and low salinity on GH/IGF axis, antioxidant response, and HPI axis in largemouth bass (Micropterus salmoides) larvae

The present study aimed to determine if low salinity could mitigate negative effects of crowding stress on freshwater largemouth bass (Micropterus salmoides). To the end, larvae were subjected to crowding stress (CS) or low salinity (LS, 0.5‰), alone or in combination for 28 days. Growth, antioxidant capacity and stress response were investigated. CS significantly reduced body weight, total antioxidant capacity (TAC) and catalase (CAT) activity in the brain and head kidney, TAC and superoxide dismutase (SOD) activity in the liver, and increased cortisol levels in the whole body, suggesting negative effects of CS on fish. Contrarily, LS promoted body weight, body length and condition factor, and reduced MDA contents in the liver and head kidney and whole-body cortisol levels. Increases in TAC and CAT activity in the brain, SOD and CAT activities in the liver, and TAC, SOD and CAT activities in the head kidney were also observed in the larvae subjected to LS. The results indicated that LS promoted growth and antioxidant capacity and reduced stress response, which was also observed in fish subjected to CS. In order to elucidate the related molecular mechanisms, gene expression in the growth hormone/insulin-like growth factor-I (GH/IGF) axis, NF-E2-related factor 2 (Nrf2) pathway, and hypothalamus–pituitary–interrenal (HPI) axis were examined. We found that CS + LS up-regulated growth hormone release hormone gene (ghrh), growth hormone gene (gh), and hormone receptor gene (ghra) in the brain and ghra and insulin-like growth factor genes (igf1 and igf2b) in the liver compared with CS alone. The mRNA levels of Nrf2 pathway related genes were sharply enhanced by CS but were maintained relative constant by CS + LS in the brain and liver compared with the control. In the head kidney, CS + LS up-regulated Nrf2 pathway related genes compared with CS alone. HPI axis related genes tended to be up-regulated by CS but remain unchanged by CS + LS compared with the control. LS and CS + LS down-regulated both genes encoding cytochrome P450 enzymes (cyp17a1 and cyp11c1) which are rate-limiting enzymes for cortisol synthesis compare with the control and CS, respectively. Taken together, the present results for the first time provide a feasible suggestion for culture of largemouth bass larvae at high stocking density in saline waters.

LED light spectra differently affected growth, antioxidant capacity, stress response, GH/IGF and HPI axis in largemouth bass (Micropterus salmoides) larvae

This study aimed to investigate the effects of white (control), blue, green and red light-emitting diodes (LEDs) spectra on the growth, antioxidant and stress response, and mRNA levels in the growth hormone/insulin-like growth factor-I (GH/IGF) axis, NF-E2-related factor 2 (Nrf2) pathway and hypothalamus–pituitary–interrenal (HPI) axis in largemouth bass (Micropterus salmoides) larvae. The blue and green LEDs significantly increased body weight and condition factor, which may be explained by increased mRNA expression of GH/IGF axis genes that encode insulin-like growth factor, growth hormone, hormone release hormone, and growth hormone receptors. The promoted antioxidant capacity was observed in the brain of fish subjected to blue LEDs and liver of fish subjected to blue and green LEDs, which may be associated with increased expression of nrf2 and its downstream genes. Both blue and green LEDs did not significantly affect cortisol levels but down-regulated several HPI axis genes. Unlike blue and green LEDs, red LED increased malondialdehyde (MDA) levels, reduced the activities of superoxide dismutase (SOD) and catalase (CAT), and total antioxidant capacity (TAC), and down-regulated Nrf2 signaling in the head kidney. Cortisol levels increased, and HPI axis was down-regulated in fish exposed to red LEDs. Taken together, blue and green LEDs had beneficial effects on growth, antioxidant capacity, and stress response via physiological and transcriptional regulation of GH/IGF axis, Nrf2 and HPI axis signaling, which may help to improve the welfare of largemouth bass in indoor recirculating water aquaculture facilities.

Effects of arginine and/or N-carbamylglutamate supplementation on growth, biochemical composition and expression of growth-regulating factors of hybrid sturgeon (Acipenser schrenckii ♀ ×A. baerii ♂) juveniles fed an arginine-deficient diet

A 2 × 3 factorial experiment was carried out to determine the roles of arginine (Arg) and/or N-carbamylglutamate (NCG) supplemented in diet on growth, biochemical composition as well as mRNA expression levels of growth hormone/insulin-like growth factor-I (GH/IGF-I) in the hybrid sturgeon (Acipenser schrenckii ♀×A. baerii ♂) juveniles raised by the Arg-deficient diet. 30 fish pre tank was fed with each diet (Arg levels: 0% and 1%; NCG levels: 0%, 0.05% and 0.1%) for 8 weeks with three replications for each group. Fish supplemented with 0.1% NCG showed significantly increased final body weight, weight gain rate and protein efficiency ratio, whereas decreased feed conversion ratio compared with those supplemented with 0% NCG (P < 0.05). Dietary Arg or NCG reduced the body moisture but elevated the body crude lipid (P < 0.05). Body crude protein content was significantly increased by the addition of 0.05% NCG (P < 0.05). The Arg concentration of the carcass was significantly affected by dietary Arg and NCG levels (P < 0.05). Dietary NCG supplementation significantly increased the NO concentrations (P < 0.05). The hepatic nitric oxide synthase (NOS) activity in fish supplemented with 0.1% NCG significantly increased relative to that in those supplemented with 0% NCG (P < 0.05). Dietary NCG supplementation markedly increased IGF-I mRNA expression level(P < 0.05). Besides, GH mRNA expression level in 0.1% NCG groups evidently increased relative to those in 0% NCG groups. These results indicated that dietary supplementation with 1% Arg and/or 0.1% NCG could improve growth performance and increase Arg concentration and the GH/IGF-1 gene expression of hybrid sturgeon fed an Arg-deficient diet.

Combined effects of polystyrene microplastics and cadmium on oxidative stress, apoptosis, and GH/IGF axis in zebrafish early life stages

The toxicological interactions of microplastics (MPs) and heavy metals have been paid much attention in aquatic organism. The mechanisms are not fully clear, particularly in fish early life stages. To the end, zebrafish embryos were exposed to 500 μg/L MPs, 5 μg/L cadmium (Cd), and their combination for 30 days. Body weight, adsorption characteristics of Cd onto MPs, Cd accumulation, oxidative stress, apoptosis, and growth hormone/insulin-like growth factor-I (GH/IGF) axis were examined. Exposure to MPs and Cd alone reduced body weight, which was aggravated by co-exposure. An increase in reactive oxygen species (ROS) levels was observed in larvae exposed to Cd or MPs + Cd, suggesting an induction of oxidative stress. Lipid peroxidation levels were not affected by exposure to MPs and Cd alone but dramatically enhanced by co-exposure, which may be explained by the reduction of total antioxidant capacity (TAOC) and activity levels of Mn-superoxide dismutase (Mn-SOD) and catalase (CAT) after co-exposure. Increased apoptotic cells were observed in the vertebral body of larvae exposed to Cd, the esophagus of larvae exposed to MPs, and both organs of larvae exposed to MPs + Cd, which was further confirmed by changes in the activities of Caspase-3, Caspase-8 and Caspase-9. PCR array on the transcription of genes related to growth, oxidative stress and apoptosis was examined, showing that the combined exposure resulted in greater magnitude of changes than MPs and Cd alone. The results indicate that MPs can enhance the negative effects of Cd on growth, oxidative damage and apoptosis in early life stages of zebrafish. However, the adsorption of Cd onto MPs was not observed and the combined exposure did not increase the Cd content in larvae compared to the single Cd exposure, implying that vector role of MPs in Cd uptake is negligible.

Population Pharmacokinetics and Pharmacodynamics of Once-Daily Growth Hormone Norditropin® in Children and Adults.

Background and ObjectiveOnce-daily injectable recombinant human growth hormone (GH) formulations (e.g. Norditropin®; Novo Nordisk A/S) are used to treat GH deficiency in children and adults, with much of the therapeutic effect mediated via the insulin-like growth factor-I (IGF-I) response. Despite a long history of use, there are few data on the pharmacokinetics and pharmacodynamics (serum IGF-I response) of this therapy, or of potential differences in the relationship of GH pharmacokinetic/pharmacodynamic (PK/PD) effects between children and adults. This study aimed to characterise the GH pharmacokinetics and IGF-I profile following daily subcutaneous GH in adults and children with GH deficiency.MethodsA model was developed based on a population PK/PD modelling meta-analysis of data from three phase I clinical trials (two using Norditropin® as a comparator with somapacitan, and one as a comparator with a pegylated GH product). Sequential model building was performed, first developing a model that could describe GH pharmacokinetics. A PD model of IGF-I data was then developed using PK and PD data, and where all PK parameters were kept fixed to those estimated in the PK model.ResultsThe model developed accurately describes and predicts GH pharmacokinetics and IGF-I response. Body weight was shown to have an important inversely correlated influence on GH exposure (and IGF-I standard deviation score), and this largely explained differences between adults and children.ConclusionsThe pharmacokinetics/pharmacodynamics developed here can inform expectations about the PD effects of different doses of GH in patients with GH deficiency of different body weights, regardless of their age.Clinical Trial RegistrationPooled modelling analysis of data from ClinicalTrials.gov identifiers NCT01973244, NCT00936403 and NCT01706783.Dates of registrationNCT01973244: 22 October, 2013; NCT00936403: 9 July, 2009; NCT01706783: 11 October, 2012.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40262-021-01011-3.

Strong Positive Correlation between TSH and Ghrelin in Euthyroid Non-Growth Hormone-Deficient Children with Short Stature.

The growth processes in children depend on the proper functioning of some hormones and growth factors. Recently, a positive correlation between ghrelin and TSH (thyroid stimulating hormone) in patients with hyper- and hypothyroidism was proved. Moreover, in hypothyroid rats with high ghrelin concentration, growth hormone (GH) and insulin-like growth factor I (IGF-I) secretion was suppressed. We analyzed these relationships in euthyroid prepubertal children with idiopathic short stature (ISS). The analysis comprised concentration of ghrelin, GH in stimulating tests and during the night, as well as IGF-I, TSH, free thyroxine (FT4) and free triiodothyronine (FT3) in 85 children with ISS (36 girls, 49 boys) aged 9.65 ± 3.02 years (mean ± SD). A strong positive correlation between ghrelin and TSH was confirmed (r = +0.44, p < 0.05). A higher ghrelin but lower nocturnal GH and lower IGF-I were observed in children with higher normal TSH concentration than those in children with lower normal TSH. Interestingly, alterations of TSH level were without any impact on FT4 and FT3 concentrations. Summing up, in ISS prepubertal euthyroid children, ghrelin and TSH secretion are closely related. On the other hand, the higher the TSH, the lower the nocturnal GH and IGF-I levels. The contribution of the above findings in deterioration of growth processes requires further studies.

The Impact of Professional Sports Activity on GH-IGF-I Axis in Relation to Testosterone Level.

The study was designed to investigate whether sports-induced elevation of testosterone level impacts on the growth hormone/insulin-like growth factor-I (GH-IGF-I) axis and body composition, especially skeletal muscle mass. The study included 12 male wrestlers aged 21.1 ± 1.7 years and 10 male nonathletes aged 21.1 ± 1.2 years. Anthropometric and biochemical measurements in the group of nonathlete men were carried out once, while for wrestlers they were carried out twice, that is, on the 1st and 14th days of the training camp.The levels of resting free testosterone (fT), cortisol (C), and human growth hormone (hGH) were significantly higher in the athletes than in nonathletes. A 2-week sports training induced a significant reduction in fT, IGF-I, and IGF binding protein-3 (IGFBP-3) levels and a rise in C level. Increased C level and reduced fT level in the athletes’ blood caused a rise in C/fT from the level of 39.95 ± 4.97 nmol/L to 59.73 ± 10.09 nmol/L (p < .05). A negative correlation was demonstrated between C/fT ratio and IGF-I level (r = −0.474, p < .05), which may indicate an inhibitory impact of high C level and low fT concentration on IGF-I release in response to sports training.Sports activity induces significant changes in the C/fT ratio that can impact on the secretion of GH and IGF-I from the liver and finally on the fat-free body mass. The quantification of GH-IGF-I axis in relation to testosterone level could be a useful diagnostic tool in biochemical assessment of the regenerative ability of skeletal muscle or provide evidence of the early stages of muscle functional overload.

Dietary raw starch to gelatinized starch ratios: Effects on the growth performance, digestive functions, intestinal histology and growth hormone‐insulin‐like growth factor‐I axis of blunt snout breamMegalobrama amblycephala

A 10-week feeding trial was conducted to investigate the effects of dietary raw starch (RS)/gelatinized starch (GS) ratios on the growth, digestive functions, intestinal histology and the growth hormone-insulin-like growth factor-I (GH-IGF-I) axis of Megalobrama amblycephala. Fish were randomly fed five diets containing various RS/GS ratios: 100/0, 75/25, 50/50, 25/75 and 0/100. Fish in the 75/25 group obtained the highest weight gain rate, specific growth rate, protein efficiency ratio and nitrogen retention efficiency compared with other groups, whereas the opposite was true for feed conversion ratio. Intestinal activities of amylase, maltase and sucrase all achieved the highest values in the 75/25 group. The highest lipase and α-glucosidase activities were found in the 25/75 and 50/50 groups respectively. Activities of protease, alkaline phosphatase and Na+,K+-ATP decreased with the decreasing of RS/GS ratios. The villi length and crypt depth of the 75/25 group were significantly higher than that of the 100/0 group. Furthermore, the transcriptions of GH increased with the decreasing of RS/GS ratios with the highest observed in the 75/25 group. Overall, our findings indicated that a RS/GS ratio of 75/25 could benefit the growth performance of Megalobrama amblycephala by increasing intestinal digestive and absorptive capabilities as well as promoting GH release.

Liver-derived IGF-I is not required for protection against osteoarthritis in male mice.

Insulin-like growth factor-I (IGF-I) is anabolic for cartilage and important for cartilage integrity, which might suggest a connection between IGF-I and osteoarthritis (OA) development. However, the results of studies performed so far are conflicting, and we aimed to clarify the role of endocrine IGF-I in rodent OA. Male mice with inducible inactivation of circulating, liver-derived IGF-I (LI-IGF-I-/- mice, serum IGF-I reduced by ~80%) were used. Experimental OA was induced in young adult LI-IGF-I-/- and control mice by destabilization of the medial meniscus (DMM); age-related OA was also evaluated in 1-yr-old mice. DMM-operated LI-IGF-I-/- mice had thinner lateral subchondral bone plate in tibia compared with control mice, whereas osteophyte volume and articular cartilage damage were unaffected at the medial side of the DMM knee. However, the control mice but not the LI-IGF-I-/- mice also developed mild OA on the lateral side of the DMM knee compared with the unoperated knee. One-year-old LI-IGF-I-/- mice had lower mid-diaphyseal cortical bone area than the 1-yr-old control mice, whereas analyses of joint tissues displayed smaller osteophyte volume and thicker calcified cartilage than the control mice. There was no difference in OA severity in the articular cartilage between old LI-IGF-I-/- and control mice. Our study is the first to investigate whether there is an association between circulating IGF-I and OA in mice. We conclude that, although there is an ~80% reduction of circulating IGF-I and a decrease in cortical bone in male LI-IGF-I-/- mice, cartilage damage is clearly not intensified and may instead be slightly reduced.

Chronic adult-onset of growth hormone/IGF-I hypersecretion improves cognitive functions and LTP and promotes neuronal differentiation in adult rats.

Besides their metabolic and endocrine functions, the growth hormone (GH) and its mediated factor, the insulin-like growth factor I (IGF-I), have been implicated in different brain functions, including neurogenesis. Long-lasting elevated GH and IGF-I levels result in non-reversible somatic, endocrine and metabolic morbidities. However, the subcutaneous implantation of the GH-secreting (GH-S) GC cell line in rats leads to the controllable over-secretion of GH and elevated IGF-I levels, allowing the experimental study of their short-term effects on brain functions. Adult rats were implanted with GC cells and checked 10weeks later, when a GH/IGF-I-secreting tumour was already formed. Tumour-bearing rats acquired different operant conditioning tasks faster and better than controls and tumour-resected groups. They also presented better retentions of long-term memories in the passive avoidance test. Experimentally evoked long-term potentiation (LTP) in the hippocampus was also larger and longer lasting in the tumour bearing than in the other groups. Chronic adult-onset of GH/IGF-I hypersecretion caused an acceleration of early progenitors, facilitating a faster neural differentiation, maturation and integration in the dentate gyrus, and increased the complexity of dendritic arbours and spine density of granule neurons. Thus, adult-onset hypersecretion of GH/IGF-I improves neurocognitive functions, long-term memories, experimental LTP and neural differentiation, migration and maturation.

Role of growth hormone in development and maintenance of follicles and corpora lutea

Growth hormone (GH) is a pituitary hormone that affects animal growth, metabolism, lactation, and reproduction. Many of the effects of GH are mediated by insulin-like growth factor I (IGF-I) which is synthesized in liver and ovary in response to GH. Insulin-like growth factor I synergizes with gonadotrophins (LH and FSH) to stimulate growth and differentiation of ovarian cells. There are species differences in the effects of GH in reproductive biology. In most species, ovarian follicles and corpora lutea are potential sites for GH action because the GH receptor is found within granulosal cells as well as corpora lutea. However, growth hormone does not control ovarian IGF-I in all species and, in ruminants, endocrine IGF-I from liver may be the principal mediator of GH action. In cattle, administration of GH increases the number of small antral ovarian follicles but does not increase the number of large antral (dominant) follicles. Growth hormone may antagonize some aspects of dominant follicular function because dominant follicles are shorter-lived in GH-treated cattle. The corpora lutea has increased growth and steroidogenesis in response to GH. Growth hormone-induced steroidogenesis in cultured granulosal and luteal cells depends on IGF-I release after GH treatment. Bovine and ovine granulosal cells do not release IGF-I in response to GH in vitro and, therefore, are less responsive to GH. These results demonstrate that GH is required for normal reproductive function in ruminant as well as nonruminant species.

Mini Review/Commentary: Growth Hormone Treatment in Children with Type 1 Diabetes.

In the state of insulin deficiency, the growth hormone—insulin-like growth factor-I (GH–IGF-I) axis is altered due to hepatic GH resistance, which leads to GH hypersecretion and low circulating IGF-I concentration. On the other hand, both growth hormone deficiency (GHD) and GH excess have significant influence on carbohydrate metabolism. These complex interactions are challenging in diagnosing GHD in subjects with type 1 diabetes mellitus (T1DM) and in treating subjects with T1DM with GH. So far, there is only limited clinical experience in GH treatment in patients with T1DM, but recently first reports on metabolic safety and efficacy of GH treatment in subjects with T1DM have been published.

Sodium Glucose Co-transporter Inhibitors in Patients with Acromegaly and Diabetes

Acromegaly per se predisposes to diabetes. Somatostatin analogs (SSAs) have an overall neutral effect on glycemic control. However, a marked increase in hyperglycemia was observed recently since the introduction of pasireotide long-acting release (PAS-LAR). Sodium glucose cotransporter inhibitors (SGLT2is) have proven their efficacy, cardiovascular safety, and superiority in the management of type 2 diabetes mellitus (T2DM). However, this class is rarely recommended for patients with diabetes and acromegaly. A decreased circulating insulin level is considered unique for this class and might have a beneficial role in the growth hormone-insulin-like growth factor-I (GH-IGF-I) axis. Therefore, SGLT2is should be considered in the management of diabetes in patients with acromegaly. This article highlights the role of this novel class for the management of diabetes in patients with acromegaly.

Growth Hormone Receptor Gene Expression Increase Reflects Nutritional Status Improvement in Patients Affected by Crohn's Disease.

Background: We proposed to verify the role of growth hormone receptor gene expression in growth failure of children with Crohn's disease (CD).Methods: We measured serum levels of growth hormone binding protein (GHBP) and insulin-like growth factor-I (IGF-I), and growth hormone receptor (GHR) gene expression in peripheral blood mononuclear cells of 21 patients with CD (before and after therapy) and in 27 age-sex-matched controls.Results: At diagnosis, significantly lower insulin-like growth factor-I and growth hormone binding protein levels were found in the CD group compared to the controls. Growth hormone receptor mRNA expression was lower in patients at diagnosis compared to the controls, even though the difference did not reach statistical significance, and significantly increased in patients in the following year. Insulin-like growth factor-I levels showed significant improvements 1 year after diagnosis compared to basal levels. On the contrary, growth hormone binding protein values had not significantly changed after 1 year of therapy.Conclusion: Our study raises the hypothesis of another mechanism through which cytokines interact with the growth hormone/insulin-like growth factor-I (GH/IGF-I) axis.

Novel functional role of GH/IGF-I in neonatal lung myofibroblasts and in rat lung growth after intrauterine growth restriction.

Intrauterine growth restriction (IUGR) is a risk factor for neonatal chronic lung disease (CLD) characterized by reduced alveoli and perturbed matrix remodeling. Previously, our group showed an activation of myofibroblasts and matrix remodeling in rat lungs after IUGR. Because growth hormone (GH) and insulin-like growth factor I (IGF-I) regulate development and growth, we queried 1) whether GH/IGF-I signaling is dysregulated in lungs after IUGR and 2) whether GH/IGF-I signaling is linked to neonatal lung myofibroblast function. IUGR was induced in Wistar rats by isocaloric low-protein diet during gestation. Lungs were obtained at embryonic day (E) 21, postnatal day (P) 3, P12, and P23. Murine embryonic fibroblasts (MEF) or primary neonatal myofibroblasts from rat lungs of control (pnFCo) and IUGR (pnFIUGR) were used for cell culture studies. In the intrauterine phase (E21), we found a reduction in GH receptor (GH-R), Stat5 signaling and IGF-I expression in lungs after IUGR. In the postnatal phase (P3-P23), catchup growth after IUGR was linked to increased GH mRNA, GH-R protein, activation of proliferative Stat5/Akt signaling, cyclin D1 and PCNA in rat lungs. On P23, a thickening of the alveolar septae was related to increased vimentin and matrix deposition, indicating fibrosis. In cell culture studies, nutrient deprivation blocked GH-R/IGF-IR signaling and proliferation in MEFs; this was reversed by IGF-I. Proliferation and Stat5 activation were increased in pnFIUGR. IGF-I and GH induced proliferation and migration of pnFCo; only IGF-I had these effects on pnFIUGR. Thus, we show a novel mechanism by which the GH/IGF-I axis in lung myofibroblasts could account for structural lung changes after IUGR.

The Impact of Initial Energy Reserves on Growth Hormone Resistance and Plasma Growth Hormone-Binding Protein Levels in Rainbow Trout Under Feeding and Fasting Conditions.

The growth hormone (GH)–insulin-like growth factor I (IGF-I) system regulates important physiological functions in salmonid fish, including hydromineral balance, growth, and metabolism. While major research efforts have been directed toward this complex endocrine system, understanding of some key aspects is lacking. The aim was to provide new insights into GH resistance and growth hormone-binding proteins (GHBPs). Fish frequently respond to catabolic conditions with elevated GH and depressed IGF-I plasma levels, a condition of acquired GH resistance. The underlying mechanisms or the functional significance of GH resistance are, however, not well understood. Although data suggest that a significant proportion of plasma GH is bound to specific GHBPs, the regulation of plasma GHBP levels as well as their role in modulating the GH–IGF-I system in fish is virtually unknown. Two in vivo studies were conducted on rainbow trout. In experiment I, fish were fasted for 4 weeks and then refed and sampled over 72 h. In experiment II, two lines of fish with different muscle adiposity were sampled after 1, 2, and 4 weeks of fasting. In both studies, plasma GH, IGF-I, and GHBP levels were assessed as well as the hepatic gene expression of the growth hormone receptor 2a (ghr2a) isoform. While most rainbow trout acquired GH resistance within 4 weeks of fasting, fish selected for high muscle adiposity did not. This suggests that GH resistance does not set in while fat reserves as still available for energy metabolism, and that GH resistance is permissive for protein catabolism. Plasma GHBP levels varied between 5 and 25 ng ml−1, with large fluctuations during both long-term (4 weeks) fasting and short-term (72 h) refeeding, indicating differentiated responses depending on prior energy status of the fish. The two opposing functions of GHBPs of prolonging the biological half-life of GH while decreasing GH availability to target tissues makes the data interpretation difficult, but nutritional regulatory mechanisms are suggested. The lack of correlation between hepatic ghr2a expression and plasma GHBP levels indicate that ghr2a assessment cannot be used as a proxy measure for GHBP levels, even if circulating GHBPs are derived from the GH receptor molecule.

The growth hormone-insulin-like growth factor-I axis in the diagnosis and treatment of growth disorders.

The growth hormone (GH)–insulin-like growth factor (IGF)-I axis is a key endocrine mechanism regulating linear growth in children. While paediatricians have a good knowledge of GH secretion and assessment, understanding and use of measurements of the components of the IGF system are less current in clinical practice. The physiological function of this axis is to increase the anabolic cellular processes of protein synthesis and mitosis, and reduction of apoptosis, with each being regulated in the appropriate target tissue. Measurement of serum IGF-I and IGF-binding protein (IGFBP)-3 concentrations can complement assessment of GH status in the investigation of short stature and contribute to prediction of growth response during GH therapy. IGF-I monitoring during GH therapy also informs the clinician about adherence and provides a safety reference to avoid over-dosing during long-term management.

The Role of Growth Hormone and Insulin-Like Growth Factor-I in the Liver.

Adult growth hormone deficiency (GHD) is characterized by metabolic abnormalities associated with visceral obesity, impaired quality of life, and increased mortality. Patients with adult GHD show increased prevalence of non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH), and growth hormone (GH) replacement therapy has been shown to improve these conditions. It has also been demonstrated that a decrease in the GH insulin-like growth factor-I (IGF-I) axis is closely associated with the progression of general NAFLD, suggesting a physiological role of these hormones for the maintenance of the liver. NASH histologically demonstrates inflammation, necrosis, and fibrosis, in addition to steatosis (and is a serious disease because it can progress to liver cirrhosis and hepatocellular carcinoma in a subset of cases). While fibrosis determines the prognosis of the patient, efficacious treatment for fibrosis is crucial; however, it has not yet been established. Recent studies have clarified the essential roles of GH and IGF-I in the liver. GH profoundly reduces visceral fat, which plays an important role in the development of NAFLD. Furthermore, GH directly reduces lipogenesis in the hepatocytes. IGF-I induces cellular senescence and inactivates hepatic stellate cells, therefore ameliorating fibrosis. IGF-I treatment has been shown to improve animal models of NASH and cirrhosis, suggesting potential clinical applications of IGF-I in these conditions. In this review, I will focus on the important roles of GH and IGF-I in the liver, their underlying mechanisms, and their potential therapeutic applications.